Ischemic Heart Disease Pathophysiology Paradigms Overview: From Plaque Activation to Microvascular Dysfunction

Ischemic heart disease still represents a large burden on individuals and health care resources worldwide. By conventions, it is equated with atherosclerotic plaque due to flow-limiting obstruction in large–medium sized coronary arteries. However, clinical, angiographic and autoptic findings suggest a multifaceted pathophysiology for ischemic heart disease and just some cases are caused by severe or complicated atherosclerotic plaques. Currently there is no well-defined assessment of ischemic heart disease pathophysiology that satisfies all the observations and sometimes the underlying mechanism to everyday ischemic heart disease ward cases is misleading. In order to better examine this complicated disease and to provide future perspectives, it is important to know and analyze the pathophysiological mechanisms that underline it, because ischemic heart disease is not always determined by atherosclerotic plaque complication. Therefore, in order to have a more complete comprehension of ischemic heart disease we propose an overview of the available pathophysiological paradigms, from plaque activation to microvascular dysfunction.

[1]  F. Fedele,et al.  Reduction in heart failure hospitalization rate during coronavirus disease 19 pandemic outbreak , 2020, ESC heart failure.

[2]  F. Fedele,et al.  Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis , 2020, Journal of Thrombosis and Thrombolysis.

[3]  Deepak L. Bhatt,et al.  2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. , 2020, European heart journal.

[4]  Coronavirus disease 2019 in Rome: was it circulating before December? , 2020, Journal of cardiovascular medicine.

[5]  F. Fedele,et al.  The role of cardiologists in the coronavirus disease 2019 pandemic. , 2020, Kardiologia polska.

[6]  C. Weber,et al.  Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science , 2020, Cardiovascular research.

[7]  F. Fedele,et al.  Left ventricular wall stress is associated with myocardial functional recovery in patients with severe aortic stenosis and systolic dysfunction undergoing transcatheter aortic valve replacement , 2020, Journal of cardiovascular medicine.

[8]  A. Baumbach,et al.  An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. , 2020, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[9]  F. Fedele,et al.  The Role of Ranolazine for the Treatment of Residual Angina beyond the Percutaneous Coronary Revascularization , 2020, Journal of clinical medicine.

[10]  F. Fedele,et al.  Management of cardiac implantable electronic device follow‐up in COVID‐19 pandemic: Lessons learned during Italian lockdown , 2020, Journal of cardiovascular electrophysiology.

[11]  Jennifer L. Bell,et al.  Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report , 2020, medRxiv.

[12]  J. Rodríguez-Peralto,et al.  SARS‐CoV‐2 endothelial infection causes COVID‐19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases , 2020, The British journal of dermatology.

[13]  M. Bifulco,et al.  Statin therapy in COVID-19 infection: much more than a single pathway , 2020, European heart journal. Cardiovascular pharmacotherapy.

[14]  F. Fedele,et al.  Susceptibility to ischaemic heart disease: Focusing on genetic variants for ATP-sensitive potassium channel beyond traditional risk factors. , 2020, European journal of preventive cardiology.

[15]  F. Fedele,et al.  Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review , 2020, Nutrients.

[16]  P. Ponikowski,et al.  Management of heart failure patients with COVID‐19: a joint position paper of the Chinese Heart Failure Association & National Heart Failure Committee and the Heart Failure Association of the European Society of Cardiology , 2020, European journal of heart failure.

[17]  Axel Haverich,et al.  Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. , 2020, The New England journal of medicine.

[18]  S. Solomon,et al.  COVID‐19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease , 2020, European journal of heart failure.

[19]  Angelo Mazza,et al.  An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study , 2020, The Lancet.

[20]  P. Theocharis,et al.  Hyperinflammatory shock in children during COVID-19 pandemic , 2020, The Lancet.

[21]  F. Gao,et al.  A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 , 2020, Science.

[22]  K. Mertz,et al.  Postmortem examination of COVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction , 2020, Histopathology.

[23]  F. Fedele,et al.  Ischemic Heart Disease and Heart Failure: Role of Coronary Ion Channels , 2020, International journal of molecular sciences.

[24]  F. Crea,et al.  COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options , 2020, Cardiovascular research.

[25]  Michele Emdin,et al.  Statin therapy in COVID-19 infection , 2020, European heart journal. Cardiovascular pharmacotherapy.

[26]  R. Bonow,et al.  Myocardial ischemia: From disease to syndrome. , 2020, International journal of cardiology.

[27]  E. Kenigsberg,et al.  Advancing scientific knowledge in times of pandemics , 2020, Nature Reviews Immunology.

[28]  M. Drazner,et al.  Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome , 2020, Circulation.

[29]  G. Lippi,et al.  Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019 , 2020, Mayo Clinic Proceedings.

[30]  Jiagao Lv,et al.  Coronavirus Disease 2019 (COVID‐19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin‐Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection , 2020, Journal of the American Heart Association.

[31]  Dong Men,et al.  Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients , 2020, medRxiv.

[32]  D. Tousoulis,et al.  ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on 'coronary microvascular dysfunction in cardiovascular disease'. , 2020, Cardiovascular research.

[33]  G. Niccoli,et al.  Myocardial and Microvascular Injury Due to Coronavirus Disease 2019 , 2020, European cardiology.

[34]  E. Prescott,et al.  Diagnosis of coronary microvascular dysfunction in the clinic. , 2020, Cardiovascular research.

[35]  C. Gaudio,et al.  Low-grade endotoxaemia enhances artery thrombus growth via Toll-like receptor 4: implication for myocardial infarction. , 2020, European heart journal.

[36]  C. Spadaccio,et al.  Changes of the coronary arteries and cardiac microvasculature with aging: Implications for translational research and clinical practice , 2019, Mechanisms of Ageing and Development.

[37]  F. Fedele,et al.  Advanced Heart Failure and End-Stage Heart Failure: Does a Difference Exist , 2019, Diagnostics.

[38]  F. Fedele,et al.  Electrocardiographic features, mapping and ablation of idiopathic outflow tract ventricular arrhythmias , 2019, Journal of Interventional Cardiac Electrophysiology.

[39]  E. Levelt,et al.  Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date , 2019, World journal of diabetes.

[40]  G. Heusch Coronary microvascular obstruction: the new frontier in cardioprotection , 2019, Basic Research in Cardiology.

[41]  C. Rapezzi,et al.  Histopathological comparison of intramural coronary artery remodeling and myocardial fibrosis in obstructive versus end-stage hypertrophic cardiomyopathy. , 2019, International journal of cardiology.

[42]  O. Delelis,et al.  Interplay between Intrinsic and Innate Immunity during HIV Infection , 2019, Cells.

[43]  P. Errante,et al.  Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection , 2019, International journal of molecular sciences.

[44]  F. Fedele,et al.  Futility in cardiology: the need for a change in perspectives , 2019, European journal of heart failure.

[45]  F. Fedele,et al.  Structural and myocardial dysfunction in heart failure beyond ejection fraction , 2019, Heart Failure Reviews.

[46]  A. LeBlanc,et al.  Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats. , 2019, Journal of visualized experiments : JoVE.

[47]  Xiao-Ming Gao,et al.  Relaxin mitigates microvascular damage and inflammation following cardiac ischemia–reperfusion , 2019, Basic Research in Cardiology.

[48]  D. Waters,et al.  HIV infection and coronary heart disease: mechanisms and management , 2019, Nature Reviews Cardiology.

[49]  F. Fedele,et al.  Prevention of Cardiovascular Disease: Screening for Magnesium Deficiency , 2019, Cardiology research and practice.

[50]  D. Hausenloy,et al.  Role of Macrophages in Cardioprotection , 2019, International journal of molecular sciences.

[51]  R. Korthuis,et al.  Reactive species-induced microvascular dysfunction in ischemia/reperfusion. , 2019, Free radical biology & medicine.

[52]  H. Jneid,et al.  Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association , 2019, Circulation.

[53]  F. Fedele,et al.  Myocardial Ischemia and Diabetes Mellitus: Role of Oxidative Stress in the Connection between Cardiac Metabolism and Coronary Blood Flow , 2019, Journal of diabetes research.

[54]  A. Henning,et al.  Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy , 2019, Circulation.

[55]  C. Ballantyne,et al.  Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol , 2019, The New England journal of medicine.

[56]  F. Fedele,et al.  Triggers for Atrial Fibrillation: The Role of Anxiety , 2019, Cardiology research and practice.

[57]  H. Bøtker,et al.  Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. , 2019, Journal of the American College of Cardiology.

[58]  Chi‐Hang Lee,et al.  Platelet inhibition to target reperfusion injury trial: Rationale and study design , 2019, Clinical cardiology.

[59]  H. Gewirtz Coronary circulation: Pressure/flow parameters for assessment of ischemic heart disease , 2019, Journal of Nuclear Cardiology.

[60]  K. Kinzler,et al.  Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome , 2018, Nature.

[61]  M. Sabatine PCSK9 inhibitors: clinical evidence and implementation , 2018, Nature Reviews Cardiology.

[62]  Kristian Thygesen,et al.  Fourth Universal Definition of Myocardial Infarction (2018). , 2018, Journal of the American College of Cardiology.

[63]  Richard D Moore,et al.  Coronary Endothelial Dysfunction Is Associated With Elevated Serum PCSK9 Levels in People With HIV Independent of Low‐Density Lipoprotein Cholesterol , 2018, Journal of the American Heart Association.

[64]  R. Kloner,et al.  No-reflow phenomenon in the heart and brain. , 2018, American journal of physiology. Heart and circulatory physiology.

[65]  C. Berry,et al.  Systemic microvascular dysfunction in microvascular and vasospastic angina , 2018, European heart journal.

[66]  Y. Park,et al.  Progression of cardiovascular autonomic neuropathy and cardiovascular disease in type 2 diabetes , 2018, Cardiovascular Diabetology.

[67]  F. Fedele,et al.  Evaluation of coronary features of HIV patients presenting with ACS: The CUORE, a multicenter study. , 2018, Atherosclerosis.

[68]  X. Tu,et al.  Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy , 2018, Acta Pharmacologica Sinica.

[69]  R. Rosenson,et al.  Systematic Review of Methods Used for the Microvascular Assessment of Peripheral Arterial Disease , 2018, Cardiovascular Drugs and Therapy.

[70]  G. Heusch,et al.  Coronary microembolization and microvascular dysfunction. , 2018, International journal of cardiology.

[71]  Sanjiv J. Shah,et al.  Association of Biomarker Clusters With Cardiac Phenotypes and Mortality in Patients With HIV Infection , 2018, Circulation. Heart failure.

[72]  Maria Laura De Marchis,et al.  Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels , 2018, International journal of molecular sciences.

[73]  A. Koller,et al.  Remodeling of Wall Mechanics and the Myogenic Mechanism of Rat Intramural Coronary Arterioles in Response to a Short-Term Daily Exercise Program: Role of Endothelial Factors , 2018, Journal of Vascular Research.

[74]  C. Pepine,et al.  Why names matter for women: MINOCA/INOCA (myocardial infarction/ischemia and no obstructive coronary artery disease) , 2018, Clinical cardiology.

[75]  S. David,et al.  Frequency of Cholesterol Crystals in Culprit Coronary Artery Aspirate During Acute Myocardial Infarction and Their Relation to Inflammation and Myocardial Injury. , 2017, The American journal of cardiology.

[76]  T. Marwick,et al.  The ageing heart: the systemic and coronary circulation , 2017, Heart.

[77]  Andrew S. Holmes,et al.  Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]) , 2017, Circulation.

[78]  P. Libby,et al.  Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease , 2017, The New England journal of medicine.

[79]  Dana K Dawson,et al.  Acute stress-induced (takotsubo) cardiomyopathy , 2017, Heart.

[80]  F. Crea,et al.  Pathophysiology of Takotsubo Syndrome , 2017, Circulation.

[81]  Xiao-Ming Gao,et al.  Microvascular leakage in acute myocardial infarction: characterization by histology, biochemistry, and magnetic resonance imaging. , 2017, American journal of physiology. Heart and circulatory physiology.

[82]  R. Virmani,et al.  Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus. , 2017, Arteriosclerosis, thrombosis, and vascular biology.

[83]  I. Drenjančević,et al.  Coronary microvascular dysfunction in diabetes mellitus , 2017, The Journal of international medical research.

[84]  F. Fedele,et al.  Heart Failure With Preserved, Mid-Range, and Reduced Ejection Fraction , 2016, Cardiology in review.

[85]  T-cell Activation and E-selectin Are Associated With Coronary Plaque in HIV-infected Young Adults , 2017, The Pediatric infectious disease journal.

[86]  J. Moon,et al.  Update on hypertrophic cardiomyopathy and a guide to the guidelines , 2016, Nature Reviews Cardiology.

[87]  K. Anastos,et al.  Trends in Cardiovascular Disease Mortality Among Persons With HIV in New York City, 2001-2012. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[88]  W. Shen,et al.  Association of decreased serum vasostatin-2 level with ischemic chronic heart failure and with MACE in 3-year follow-up: Vasostatin-2 prevents heart failure in myocardial infarction rats. , 2016, International journal of cardiology.

[89]  Qiuyue Kong,et al.  HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism , 2016, Scientific Reports.

[90]  Xiao-hua Wang,et al.  Relationship between platelet-leukocyte aggregation and myocardial perfusion in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention. , 2016, Heart & lung : the journal of critical care.

[91]  M. Bukrinsky,et al.  Interaction Between HIV-1 Nef and Calnexin: From Modeling to Small Molecule Inhibitors Reversing HIV-Induced Lipid Accumulation , 2016, Arteriosclerosis, Thrombosis and Vascular Biology.

[92]  R. Kanďár,et al.  Fatty acid profile in erythrocyte membranes and plasma phospholipids affects significantly the extent of inflammatory response to coronary stent implantation. , 2016, Physiological research.

[93]  C. Gleissner,et al.  Galectin-3 binding protein plasma levels are associated with long-term mortality in coronary artery disease independent of plaque morphology. , 2016, Atherosclerosis.

[94]  H. Niessen,et al.  Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction , 2016, PloS one.

[95]  E. Bruckert,et al.  Cardiovascular Disease Risk Associated With Familial Hypercholesterolemia: A Systematic Review of the Literature. , 2016, Clinical therapeutics.

[96]  Morten Wang Fagerland,et al.  Circulating Levels of IL‐6 Receptor and gp130 and Long‐Term Clinical Outcomes in ST‐Elevation Myocardial Infarction , 2016, Journal of the American Heart Association.

[97]  R. Feldman Heart Disease in Women: Unappreciated Challenges, GPER as a New Target , 2016, International journal of molecular sciences.

[98]  M. Grant,et al.  Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure. , 2016, Circulation research.

[99]  G. Niccoli,et al.  Coronary microvascular obstruction in acute myocardial infarction. , 2016, European heart journal.

[100]  N. Nader,et al.  Statin drugs mitigate cellular inflammatory response after ST elevation myocardial infarction, but do not affect in-hospital mortality , 2016, Journal of cardiovascular and thoracic research.

[101]  M. Freiberg,et al.  HIV and Cardiovascular Disease: We Need a Mechanism, and We Need a Plan , 2016, Journal of the American Heart Association.

[102]  S. Grinspoon,et al.  Pathophysiology and Management of Cardiovascular Disease in HIV-Infected Patients , 2016, The lancet. Diabetes & endocrinology.

[103]  A. Pries,et al.  Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation. , 2015, European heart journal.

[104]  M. Nieminen,et al.  Pharmaco-economics of levosimendan in cardiology: a European perspective. , 2015, International journal of cardiology.

[105]  J. Mehta,et al.  LOX-1 in macrophage migration in response to ox-LDL and the involvement of calpains. , 2015, Biochemical and biophysical research communications.

[106]  S. Y-Hassan Post-ischemic myocardial stunning was the starting point of takotsubo syndrome: Restitution is justified after falling down on. , 2015, International journal of cardiology.

[107]  P. Kuppusamy,et al.  Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation. , 2015, Circulation research.

[108]  J. Mehta,et al.  Cross-talk between LOX-1 and PCSK9 in vascular tissues. , 2015, Cardiovascular research.

[109]  M. Clauss,et al.  Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat. , 2015, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[110]  H. Shimokawa,et al.  2015 ATVB Plenary Lecture: translational research on rho-kinase in cardiovascular medicine. , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[111]  F. Crea,et al.  Sex differences in mechanisms, presentation and management of ischaemic heart disease. , 2015, Atherosclerosis.

[112]  F. Romeo,et al.  Oxidized LDL attenuates protective autophagy and induces apoptotic cell death of endothelial cells: Role of oxidative stress and LOX-1 receptor expression. , 2015, International journal of cardiology.

[113]  F. Fedele,et al.  PATHOPHYSIOLOGY OF ACUTE CORONARY SYNDROME IN HIV POSITIVE PATIENTS: INSIGHT FROM VIRTUAL HISTOLOGY ANALYSIS , 2015 .

[114]  J. Canty,et al.  Regulation of coronary blood flow in health and ischemic heart disease. , 2015, Progress in cardiovascular diseases.

[115]  Yan Zhang,et al.  Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy. , 2015, American journal of physiology. Heart and circulatory physiology.

[116]  F. Fedele,et al.  Intramyocardial Hemorrhage: An Enigma for Cardiac MRI? , 2015, BioMed research international.

[117]  P. Camici,et al.  The role of T and B cells in human atherosclerosis and atherothrombosis , 2015, Clinical and experimental immunology.

[118]  Ornella Rimoldi,et al.  Coronary microvascular dysfunction: mechanisms and functional assessment , 2015, Nature Reviews Cardiology.

[119]  N. Wu,et al.  Inhibition of Rho-kinase by fasudil restores the cardioprotection of ischemic postconditioninng in hypercholesterolemic rat heart. , 2014, Molecular medicine reports.

[120]  J. DiNicolantonio,et al.  Prognostic indicators for recurrent thrombotic events in HIV-infected patients with acute coronary syndromes: use of registry data from 12 sites in Europe, South Africa and the United States. , 2014, Thrombosis research.

[121]  L. Hurley,et al.  HIV infection and incidence of ischemic stroke , 2014, AIDS.

[122]  H. White,et al.  Prognosis of Patients With Non–ST-Segment–Elevation Myocardial Infarction and Nonobstructive Coronary Artery Disease: Propensity-Matched Analysis From the Acute Catheterization and Urgent Intervention Triage Strategy Trial , 2014, Circulation. Cardiovascular interventions.

[123]  F. Fedele,et al.  Heart failure: TNM-like classification. , 2014, Journal of the American College of Cardiology.

[124]  F. Crea,et al.  Coronary microvascular dysfunction in patients without myocardial diseases and obstructive atherosclerosis , 2014 .

[125]  H. Bøtker,et al.  The role of capillary transit time heterogeneity in myocardial oxygenation and ischemic heart disease , 2014, Basic Research in Cardiology.

[126]  Christopher J. L. Murray,et al.  Temporal Trends in Ischemic Heart Disease Mortality in 21 World Regions, 1980 to 2010: The Global Burden of Disease 2010 Study , 2013, Circulation.

[127]  P. Fülöp,et al.  Dynamic interplay between metabolic syndrome and immunity. , 2014, Advances in experimental medicine and biology.

[128]  F. Fedele,et al.  Role of ion channels in coronary microcirculation: a review of the literature. , 2013, Future cardiology.

[129]  J. Frostegård Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2 , 2013, Front. Endocrinol..

[130]  F. Fedele,et al.  Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease , 2013, Basic Research in Cardiology.

[131]  W. Koch,et al.  Adrenergic Nervous System in Heart Failure: Pathophysiology and Therapy , 2013, Circulation research.

[132]  D. Schwenke,et al.  Acute Rho-kinase inhibition improves coronary dysfunction in vivo, in the early diabetic microcirculation , 2013, Cardiovascular Diabetology.

[133]  P. Camici,et al.  Coronary microvascular dysfunction in primary cardiomyopathies , 2013, Heart.

[134]  V. Ortiz de la Tabla,et al.  Increased Carotid Intima-Media Thickness Associated with Antibody Responses to Varicella-Zoster Virus and Cytomegalovirus in HIV-Infected Patients , 2013, PloS one.

[135]  M. Budoff,et al.  HIV infection and the risk of acute myocardial infarction. , 2013, JAMA internal medicine.

[136]  Randall C. Thompson,et al.  Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations , 2013, The Lancet.

[137]  Jeffrey A. Jones,et al.  Gene targeting in ischemic heart disease and failure: translational and clinical studies. , 2013, Biochemical pharmacology.

[138]  R. Bonow,et al.  Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link! , 2012, Journal of the American College of Cardiology.

[139]  E. Jones,et al.  Cardiac syndrome X and microvascular coronary dysfunction. , 2012, Trends in cardiovascular medicine.

[140]  S. Abbara,et al.  Arterial inflammation in patients with HIV. , 2012, JAMA.

[141]  Jeffrey N. Martin,et al.  The association of CD4+ T-cell counts and cardiovascular risk in treated HIV disease , 2012, AIDS.

[142]  O. Rimoldi,et al.  The coronary circulation and blood flow in left ventricular hypertrophy. , 2012, Journal of molecular and cellular cardiology.

[143]  Mark Woodward,et al.  Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies , 2012 .

[144]  C. Cametti,et al.  Hemocompatibility of stent materials: alterations in electrical parameters of erythrocyte membranes , 2012, Vascular health and risk management.

[145]  A. Huqi,et al.  Coronary vasospasm and coronary atherosclerosis: do we have to choose? , 2012, Journal of the American College of Cardiology.

[146]  Jeroen J. Bax,et al.  ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation , 2012 .

[147]  R. Blankstein,et al.  Quantitative relationship between the extent and morphology of coronary atherosclerotic plaque and downstream myocardial perfusion. , 2011, Journal of the American College of Cardiology.

[148]  Andrés Íñiguez,et al.  Modulación del sistema betaadrenérgico durante el infarto agudo de miocardio: justificación para un nuevo ensayo clínico , 2011 .

[149]  L. Kuller,et al.  Risk of heart failure with human immunodeficiency virus in the absence of prior diagnosis of coronary heart disease. , 2011, Archives of internal medicine.

[150]  J. Hochman,et al.  Women have less severe and extensive coronary atherosclerosis in fatal cases of ischemic heart disease: an autopsy study. , 2011, American heart journal.

[151]  F. Fedele,et al.  Cardiovascular risk factors and HIV disease. , 2011, AIDS reviews.

[152]  L. Lerman,et al.  Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction. , 2011, American journal of physiology. Heart and circulatory physiology.

[153]  [Modulation of the beta-adrenergic system during acute myocardial infarction: rationale for a new clinical trial]. , 2011, Revista espanola de cardiologia.

[154]  W. Chilian,et al.  Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative stress. , 2010, World journal of cardiology.

[155]  M. Russo,et al.  High prevalence of intramural coronary infection in patients with drug-resistant cardiac syndrome X: comparison with chronic stable angina and normal controls , 2010, Heart.

[156]  Carl J Pepine,et al.  Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. , 2010, Journal of the American College of Cardiology.

[157]  A. Rebuzzi,et al.  Reversible coronary microvascular dysfunction: a common pathogenetic mechanism in Apical Ballooning or Tako-Tsubo Syndrome. , 2010, European heart journal.

[158]  Chi‐Hang Lee,et al.  Microvascular obstruction after percutaneous coronary intervention , 2009, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[159]  C. Catalano,et al.  Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. , 2009, Journal of the American College of Cardiology.

[160]  W. J. Boscardin,et al.  Effect of Supersaturated Oxygen Delivery on Infarct Size After Percutaneous Coronary Intervention in Acute Myocardial Infarction , 2009, Circulation. Cardiovascular interventions.

[161]  E. Zakynthinos,et al.  Inflammatory biomarkers in coronary artery disease. , 2009, Journal of cardiology.

[162]  F. Van de Werf,et al.  Impact of myocardial haemorrhage on left ventricular function and remodelling in patients with reperfused acute myocardial infarction. , 2009, European heart journal.

[163]  Carl J Pepine,et al.  Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. , 2009, Archives of internal medicine.

[164]  Michael Höpfner,et al.  Structural Adaptation and Heterogeneity of Normal and Tumor Microvascular Networks , 2009, PLoS Comput. Biol..

[165]  A. Pries,et al.  Origins of heterogeneity in tissue perfusion and metabolism. , 2009, Cardiovascular research.

[166]  E. K. Weir,et al.  The metabolic basis of vascular oxygen sensing: diversity, compartmentalization, and lessons from cancer. , 2008, American journal of physiology. Heart and circulatory physiology.

[167]  R. Bache,et al.  Regulation of coronary blood flow during exercise. , 2008, Physiological reviews.

[168]  W. J. van der Giessen,et al.  Functional and Structural Adaptations of Coronary Microvessels Distal to a Chronic Coronary Artery Stenosis , 2008, Circulation research.

[169]  W. Guo,et al.  Association between baseline neutrophil count, clopidogrel therapy, and clinical and angiographic outcomes in patients with ST-elevation myocardial infarction receiving fibrinolytic therapy. , 2008, European heart journal.

[170]  M. Marzilli Coronary microcirculation : the new frontier in coronary artery disease , 2008 .

[171]  Andre Terzic,et al.  Defective Metabolic Signaling in Adenylate Kinase AK1 Gene Knock-out Hearts Compromises Post-ischemic Coronary Reflow* , 2007, Journal of Biological Chemistry.

[172]  S. Gabriel,et al.  C-reactive protein and heart failure after myocardial infarction in the community. , 2007, The American journal of medicine.

[173]  F. Crea,et al.  Coronary microvascular dysfunction. , 2013, The New England journal of medicine.

[174]  M. Robson,et al.  Evidence for Microvascular Dysfunction in Hypertrophic Cardiomyopathy: New Insights From Multiparametric Magnetic Resonance Imaging , 2007, Circulation.

[175]  B. Gersh,et al.  Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both? , 2007, European heart journal.

[176]  T. Rabelink,et al.  Endothelial function and dysfunction: testing and clinical relevance. , 2007, Circulation.

[177]  R. Bryan,et al.  H2O2 activates redox- and 4-aminopyridine-sensitive Kv channels in coronary vascular smooth muscle. , 2007, American journal of physiology. Heart and circulatory physiology.

[178]  A. Voss,et al.  Detection of Coronary Microembolization by Doppler Ultrasound in Patients With Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Interventions , 2007, Circulation.

[179]  R. Bryan,et al.  H 2 O 2 activates redox-and 4-aminopyridine-sensitive Kv channels in coronary vascular smooth muscle , 2007 .

[180]  J. Tune,et al.  Hydrogen Peroxide: A Feed-Forward Dilator That Couples Myocardial Metabolism to Coronary Blood Flow , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[181]  J. Tune Withdrawal of vasoconstrictor influences in local metabolic coronary vasodilation. , 2006, American journal of physiology. Heart and circulatory physiology.

[182]  J. Liao,et al.  Physiological role of ROCKs in the cardiovascular system. , 2006, American journal of physiology. Cell physiology.

[183]  Sujoy Khan Acute oxygen-sensing mechanisms. , 2006, The New England journal of medicine.

[184]  J. López-Barneo,et al.  Acute oxygen-sensing mechanisms. , 2005, The New England journal of medicine.

[185]  A. Voss,et al.  Detection of coronary microembolisation by Doppler ultrasound during percutaneous coronary interventions , 2005, Heart.

[186]  F. Kajiya,et al.  Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[187]  S. Gupte,et al.  Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[188]  F. Kajiya,et al.  Coronary microcirculation: Physiology and mechanics , 2005 .

[189]  P. Libby,et al.  Pathophysiology of Coronary Artery Disease , 2005, Circulation.

[190]  G. Hansson Inflammation, atherosclerosis, and coronary artery disease. , 2005, The New England journal of medicine.

[191]  S. Archer,et al.  Hypoxic pulmonary vasoconstriction: redox regulation of O2-sensitive K+ channels by a mitochondrial O2-sensor in resistance artery smooth muscle cells. , 2004, Journal of molecular and cellular cardiology.

[192]  G. Jackson Endothelial function and dysfunction , 2004, International journal of clinical practice.

[193]  A. Kirtane,et al.  Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction. , 2004, The American journal of cardiology.

[194]  Deepak L. Bhatt,et al.  Inflammation and atherosclerosis , 2004, Current atherosclerosis reports.

[195]  K. Smith,et al.  Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women: Results From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE) , 2004, Circulation.

[196]  A. Maseri Mechanisms of myocardial ischemia , 1990, Cardiovascular Drugs and Therapy.

[197]  Rodolphe Thiébaut,et al.  Combination antiretroviral therapy and the risk of myocardial infarction , 2003 .

[198]  I. Olivotto,et al.  Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. , 2003, The New England journal of medicine.

[199]  G. Heusch,et al.  Serum but not myocardial TNF-alpha concentration is increased in pacing-induced heart failure in rabbits. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[200]  Daniel Steinberg,et al.  Atherogenesis in perspective: Hypercholesterolemia and inflammation as partners in crime , 2002, Nature Medicine.

[201]  P. Ridker,et al.  Inflammatory bio‐markers and cardiovascular risk prediction , 2002, Journal of internal medicine.

[202]  Toru Suzuki,et al.  Diagnostic implications of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary artery disease. , 2002, Clinical biochemistry.

[203]  T. Sawamura,et al.  LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis. , 2002, Pharmacology & therapeutics.

[204]  J. Mehta,et al.  Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor. , 2002, Journal of the American College of Cardiology.

[205]  P. Libby,et al.  Inflammation and Atherosclerosis , 2002, Circulation.

[206]  Pepine,et al.  Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. , 2001, American heart journal.

[207]  George A. Diamond,et al.  Peripheral Arterial Responses to Treadmill Exercise Among Healthy Subjects and Atherosclerotic Patients , 2001, Circulation.

[208]  T. Matsuo,et al.  Elevated Levels of Oxidized Low Density Lipoprotein Show a Positive Relationship With the Severity of Acute Coronary Syndromes , 2001, Circulation.

[209]  P. Libby,et al.  Inflammation and thrombosis: the clot thickens. , 2001, Circulation.

[210]  E. Braunwald,et al.  Association Between White Blood Cell Count, Epicardial Blood Flow, Myocardial Perfusion, and Clinical Outcomes in the Setting of Acute Myocardial Infarction: A Thrombolysis In Myocardial Infarction 10 Substudy , 2000, Circulation.

[211]  M. Ellestad,et al.  Prevalence of patent foramen ovale in patients with acute myocardial infarction and angiographically normal coronary arteries. , 2000, The American journal of cardiology.

[212]  K. Shirato,et al.  Coronary microcirculation: physiology and pharmacology. , 2000, Pharmacology & therapeutics.

[213]  O. Hess,et al.  alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. , 2000, Circulation.

[214]  D. Granger,et al.  Pathophysiology of ischaemia–reperfusion injury , 2000, The Journal of pathology.

[215]  A. Maseri,et al.  The variable role of inflammation in acute coronary syndromes and in restenosis. , 1999, Seminars in interventional cardiology : SIIC.

[216]  A. Maseri,et al.  Pathogenic mechanisms in unstable angina , 1999, Heart.

[217]  F. Burzotta,et al.  Homocysteine and arterial occlusive disease: a concise review. , 1999, Cardiologia.

[218]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[219]  G. Ottaviani,et al.  Proliferating cell nuclear antigen (PCNA) and apoptosis in hyperacute and acute myocardial infarction. , 1999, European journal of histochemistry : EJH.

[220]  C. Tiefenbacher,et al.  Heterogeneity of coronary vasomotion , 1998, Basic Research in Cardiology.

[221]  M. Lindsey,et al.  Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. , 1998, Circulation.

[222]  E. Gurfinkel,et al.  Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study , 1997, The Lancet.

[223]  A. Camm,et al.  Elevated Chlamydia pneumoniae Antibodies, Cardiovascular Events, and Azithromycin in Male Survivors of Myocardial Infarction , 1997 .

[224]  W. Chilian Coronary microcirculation in health and disease. Summary of an NHLBI workshop. , 1997, Circulation.

[225]  R. Bohle,et al.  Tumor necrosis factor-α in macrophages of heart, liver, kidney, and in the pituitary gland , 1996, Cell and Tissue Research.

[226]  J. Muller,et al.  Triggering Myocardial Infarction by Sexual Activity: Low Absolute Risk and Prevention by Regular Physical Exertion , 1996 .

[227]  J. Muller,et al.  Triggering myocardial infarction by sexual activity. Low absolute risk and prevention by regular physical exertion. Determinants of Myocardial Infarction Onset Study Investigators. , 1996, JAMA.

[228]  T. Paavonen,et al.  Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. , 1995, Circulation.

[229]  A. Rebuzzi,et al.  The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. , 1994, The New England journal of medicine.

[230]  V. Fuster,et al.  Macrophage Infiltration in Acute Coronary Syndromes: Implications for Plaque Rupture , 1994, Circulation.

[231]  J. Koyama,et al.  Intravascular ultrasound detection of atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed coronary segments. , 1994, Journal of the American College of Cardiology.

[232]  L. Opie,et al.  Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias , 1994, The Lancet.

[233]  A. Becker,et al.  Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. , 1994, Circulation.

[234]  J. Coligan,et al.  Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. , 1993, Journal of immunology.

[235]  J I Hoffman,et al.  Pressure-flow relations in coronary circulation. , 1990, Physiological reviews.

[236]  P. Ganz,et al.  Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. , 1986, The New England journal of medicine.

[237]  E. Feigl,et al.  Coronary physiology. , 1983, Physiological reviews.

[238]  T. M. James Angina Without Coronary Disease (sic) , 1970, Circulation.

[239]  M. Prinzmetal,et al.  Angina pectoris. I. A variant form of angina pectoris; preliminary report. , 1959, The American journal of medicine.