Whole blood microRNA expression associated with stroke: Results from the Framingham Heart Study

Emerging evidence suggests microRNAs (miRNAs) may play an important role in explaining variation in stroke risk and recovery in humans, yet there are still few longitudinal studies examining the association between whole blood miRNAs and stroke. Accounting for multiple testing and adjusting for potentially confounding technical and clinical variables, here we show that whole blood miR-574-3p expression was significantly lower in participants with chronic stroke compared to non-cases. To explore the functional relevance of our findings, we analyzed miRNA-mRNA whole blood co-expression, pathway enrichment, and brain tissue gene expression. Results suggest miR-574-3p is involved in neurometabolic and chronic neuronal injury response pathways, including brain gene expression of DBNDD2 and ELOVL1. These results suggest miR-574-3p plays a role in regulating chronic brain and systemic cellular response to stroke and thus may implicate miR-574-3p as a partial mediator of long-term stroke outcomes.

[1]  William A. Li,et al.  The role of microRNA in neuronal inflammation and survival in the post ischemic brain: a review , 2017, Neurological research.

[2]  D. Levy,et al.  Stroke and Circulating Extracellular RNAs , 2017, Stroke.

[3]  R. D'Agostino,et al.  Revised Framingham Stroke Risk Profile to Reflect Temporal Trends , 2017, Circulation.

[4]  M. Fornage,et al.  Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association , 2017, Circulation.

[5]  D. Levy,et al.  Messenger RNA and MicroRNA transcriptomic signatures of cardiometabolic risk factors , 2017, BMC Genomics.

[6]  D. Levy,et al.  Discordant Expression of Circulating microRNA from Cellular and Extracellular Sources , 2016, PloS one.

[7]  Mark Gerstein,et al.  Diverse human extracellular RNAs are widely detected in human plasma , 2016, Nature Communications.

[8]  C. Fox,et al.  Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study. , 2015, Journal of hepatology.

[9]  Hermona Soreq,et al.  Checks and balances on cholinergic signaling in brain and body function , 2015, Trends in Neurosciences.

[10]  C. Belka,et al.  Circulating microRNAs as prognostic therapy biomarkers in head and neck cancer patients , 2015, British Journal of Cancer.

[11]  Andrew D. Johnson,et al.  Dissecting the Roles of MicroRNAs in Coronary Heart Disease via Integrative Genomic Analyses , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[12]  W. Kernan,et al.  Response to letter regarding article, "Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association". , 2015, Stroke.

[13]  R. Wanders,et al.  Enzymatic characterization of ELOVL1, a key enzyme in very long-chain fatty acid synthesis. , 2015, Biochimica et biophysica acta.

[14]  Chunbing Zhang,et al.  Identification of Circulating MicroRNAs as Potential Biomarkers for Detecting Acute Ischemic Stroke , 2014, Cellular and Molecular Neurobiology.

[15]  Yanjun Zeng,et al.  Circulating microRNAs as novel potential biomarkers for early diagnosis of acute stroke in humans. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[16]  S. Tan,et al.  Circulating microRNAs as potential non-invasive biomarkers for the early detection of hypertension-related stroke , 2014, Journal of Human Hypertension.

[17]  C. Bouchard,et al.  Competing targets of microRNA-608 affect anxiety and hypertension , 2014, Human molecular genetics.

[18]  D. Levy,et al.  Relations between circulating microRNAs and atrial fibrillation: data from the Framingham Offspring Study. , 2014, Heart rhythm.

[19]  K. Tan,et al.  Molecular Sciences Circulating Micrornas as Biomarkers of Acute Stroke , 2022 .

[20]  Andrew E Moran,et al.  Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010 , 2013, The Lancet. Global health.

[21]  A. Fischer,et al.  MicroRNAs as biomarkers for CNS disease , 2013, Front. Mol. Neurosci..

[22]  Xia Yang,et al.  A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[23]  Jing Wang,et al.  WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013 , 2013, Nucleic Acids Res..

[24]  Ling Liu,et al.  MicroRNA alterations in senescent endothelial progenitor cells induced by remnant-like lipoproteins. , 2012, Chinese medical journal.

[25]  J. Schneider,et al.  Overview and findings from the religious orders study. , 2012, Current Alzheimer research.

[26]  J. Schneider,et al.  Overview and findings from the rush Memory and Aging Project. , 2012, Current Alzheimer research.

[27]  F. Hamdy,et al.  Changes in circulating microRNA levels associated with prostate cancer , 2012, British Journal of Cancer.

[28]  S. Khanna,et al.  MicroRNA in ischemic stroke etiology and pathology. , 2011, Physiological genomics.

[29]  Udo Hoffmann,et al.  Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits , 2011, PLoS genetics.

[30]  J. Freedman,et al.  The distribution of circulating microRNA and their relation to coronary disease , 2010, F1000Research.

[31]  E. Olson,et al.  MicroRNAs add a new dimension to cardiovascular disease. , 2010, Circulation.

[32]  F. Sharp,et al.  Brain and Blood microRNA Expression Profiling of Ischemic Stroke, Intracerebral Hemorrhage, and Kainate Seizures , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[33]  Fang-Chi Hsu,et al.  Hepatic Steatosis and Subclinical Cardiovascular Disease in a Cohort Enriched for Type 2 Diabetes: The Diabetes Heart Study , 2008, The American Journal of Gastroenterology.

[34]  D. Bennett,et al.  Sex-dependent association of a common low-density lipoprotein receptor polymorphism with RNA splicing efficiency in the brain and Alzheimer's disease. , 2007, Human molecular genetics.

[35]  S. Pocock,et al.  Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies , 2007, BMJ : British Medical Journal.

[36]  P. Gtzsche,et al.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies , 2007, Annals of Internal Medicine.

[37]  Turgut Tatlisumak,et al.  Acute ischemic stroke: Overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia , 2007, Pharmacology Biochemistry and Behavior.

[38]  Sudha Seshadri,et al.  Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years. , 2006, JAMA.

[39]  C. Croce,et al.  MicroRNA-cancer connection: the beginning of a new tale. , 2006, Cancer research.

[40]  J. Kuret,et al.  Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1. , 2006, Biochemistry.

[41]  H. Pehamberger,et al.  The human orthologue of a novel apoptosis response gene induced during rat myelomonocytic stem cell apoptosis maps to 20q13.12. , 2005, Stem cells and development.

[42]  C. Sudlow,et al.  Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration. International Stroke Incidence Collaboration. , 1997, Stroke.

[43]  S. Thompson.  Advances in experimental medicine and biology , 1996 .

[44]  R B D'Agostino,et al.  Stroke severity in atrial fibrillation. The Framingham Study. , 1996, Stroke.

[45]  W. Kannel,et al.  An investigation of coronary heart disease in families. The Framingham offspring study. , 1979, American journal of epidemiology.

[46]  P. Wolf,et al.  Occult impaired cardiac function, congestive heart failure, and risk of thrombotic stroke: the Framingham Study. , 1970, Neurology.

[47]  Peng-tao Lin,et al.  MicroRNA-574-5p promotes cell growth of vascular smooth muscle cells in the progression of coronary artery disease. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[48]  Nada Esa,et al.  Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study). , 2015, Heart rhythm.

[49]  L. Tan,et al.  Association between stroke and Alzheimer's disease: systematic review and meta-analysis. , 2015, Journal of Alzheimer's disease : JAD.

[50]  P. Cimflova,et al.  microRNAs in Cerebrovascular Disease. , 2015, Advances in experimental medicine and biology.

[51]  V. Chair,et al.  Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. , 2014, Stroke.

[52]  Thomas Tuschl,et al.  MicroRNAs in human cancer. , 2013, Advances in experimental medicine and biology.

[53]  A Heinrichs,et al.  PubMed Central. , 2001, Trends in molecular medicine.

[54]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[55]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..