Effect of Inflammation on the Aging Microcirculation: Impact on Skeletal Muscle Blood Flow Control

To meet the metabolic demands of skeletal muscle, the vasculature supplying these vascular beds has to be connected to respond in a coordinated uniform manner, thus providing the necessary oxygen and nutrients during increased activity. The skeletal muscle microcirculation is the major resistance network controlling vascular blood supply and it is the integrity of the endothelium lining the blood vessels that is paramount in facilitating this action. Aging is a major risk factor for cardiovascular disease and is associated with significant increases in inflammatory agents that negatively impact the vasculature. Several inflammatory agents such as cytokines (tumor necrosis factor‐α), advanced glycation products (AGEs), and matrix metalloproteinases (MMPs) along with storage cells for inflammatory mediators (mast cells) are associated with a chronic “low‐grade inflammation” state that has been observed over the course of the aging process. Current research suggests that these age‐related increases in inflammatory agents can disrupt the microvascular endothelium and thus impair blood flow. This impairment could exacerbate the common age‐related disease states such as hypertension, diabetes, congestive heart failure, and sarcopenia, leading to increased mortality and morbidity.

[1]  Donald G Welsh,et al.  Defining electrical communication in skeletal muscle resistance arteries: a computational approach , 2005, The Journal of physiology.

[2]  S. Vannucci,et al.  Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. , 2005, Glycobiology.

[3]  M. Chanson,et al.  Gap junctional communication in tissue inflammation and repair. , 2005, Biochimica et biophysica acta.

[4]  Bente Klarlund Pedersen,et al.  The anti-inflammatory effect of exercise. , 2005, Journal of applied physiology.

[5]  J. Feely,et al.  Aging is associated with increased matrix metalloproteinase-2 activity in the human aorta. , 2005, American journal of hypertension.

[6]  S. Bender,et al.  Hypertension attenuates cell-to-cell communication in hamster retractor muscle feed arteries. , 2005, American journal of physiology. Heart and circulatory physiology.

[7]  S. Segal,et al.  Regulation of Blood Flow in the Microcirculation , 2005, Microcirculation.

[8]  G. W. Payne,et al.  Arteriolar network architecture and vasomotor function with ageing in mouse gluteus maximus muscle , 2004, The Journal of physiology.

[9]  C. Hill,et al.  Vascular gap junctions and implications for hypertension , 2004, Clinical and experimental pharmacology & physiology.

[10]  G. W. Payne,et al.  Connexin expression and conducted vasodilation along arteriolar endothelium in mouse skeletal muscle. , 2004, Journal of applied physiology.

[11]  S. Segal,et al.  Neural control of muscle blood flow during exercise. , 2004, Journal of applied physiology.

[12]  Elisabetta Dejana,et al.  Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. , 2004, Physiological reviews.

[13]  G. W. Payne,et al.  Histamine inhibits conducted vasodilation through endothelium‐derived NO production in arterioles of mouse skeletal muscle , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  C. Hill,et al.  Expression of homocellular and heterocellular gap junctions in hamster arterioles and feed arteries. , 2003, Cardiovascular research.

[15]  R. D'Agostino,et al.  Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. , 2003, The American journal of medicine.

[16]  E. Lakatta,et al.  Aging Increases Aortic MMP‐2 Activity and Angiotensin II in Nonhuman Primates , 2003, Hypertension.

[17]  Bente Klarlund Pedersen,et al.  Exercise and IL‐6 infusion inhibit endotoxin‐induced TNF‐α production in humans , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  Cor de Wit,et al.  Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion. , 2003, Physiological genomics.

[19]  E. Eldrup,et al.  Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes , 2003, Mechanisms of Ageing and Development.

[20]  D. Schoenfeld,et al.  PECAM-1 promotes beta-catenin accumulation and stimulates endothelial cell proliferation. , 2003, Biochemical and biophysical research communications.

[21]  P. Toutouzas,et al.  Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment , 2003, Journal of Human Hypertension.

[22]  J. Madri,et al.  Platelet-endothelial cell adhesion molecule-1 modulates endothelial migration through its immunoreceptor tyrosine-based inhibitory motif. , 2003, Biochemical and biophysical research communications.

[23]  S. Suter,et al.  Src Signaling Links Mediators of Inflammation to Cx43 Gap Junction Channels in Primary and Transformed CFTR-Expressing Airway Cells , 2003, Cell communication & adhesion.

[24]  J. Manson,et al.  Interrelationships Among Circulating Interleukin-6, C-Reactive Protein, and Traditional Cardiovascular Risk Factors in Women , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[25]  D. Shasby,et al.  Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[26]  J. Elrod,et al.  Extracellular matrix, junctional integrity and matrix metalloproteinase interactions in endothelial permeability regulation * , 2002, Journal of anatomy.

[27]  A. Newman,et al.  Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[28]  H. Y. Chung,et al.  Oxidative stress and vascular aging. , 2001, Diabetes research and clinical practice.

[29]  K. Otero,et al.  Albumin-derived advanced glycation end-products trigger the disruption of the vascular endothelial cadherin complex in cultured human and murine endothelial cells. , 2001, The Biochemical journal.

[30]  D. Lidington,et al.  Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar conducted response in vivo. , 2001, American journal of physiology. Heart and circulatory physiology.

[31]  P. Ridker,et al.  Blood Pressure and Inflammation in Apparently Healthy Men , 2001, Hypertension.

[32]  R. Rumbaut,et al.  Age-related responses of the microcirculation to ischemia-reperfusion and inflammation. , 2001, Pathophysiology : the official journal of the International Society for Pathophysiology.

[33]  H. Chung,et al.  The Inflammation Hypothesis of Aging , 2001 .

[34]  K. Yarasheski,et al.  Resistance exercise decreases skeletal muscle tumor necrosis factor α in frail elderly humans , 2001 .

[35]  P. Lampe,et al.  Regulation of gap junctions by phosphorylation of connexins. , 2000, Archives of biochemistry and biophysics.

[36]  J. van de Voorde,et al.  The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin – induced diabetic rats is restored by 5-methyltetrahydrofolate , 2000, Diabetologia.

[37]  W. Ehringer,et al.  Bradykinin and α-Thrombin Increase Human Umbilical Vein Endothelial Macromolecular Permeability by Different Mechanisms , 2000, Inflammation.

[38]  K. Willecke,et al.  Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. , 2000, Circulation research.

[39]  G. G. Emerson,et al.  Endothelial cell pathway for conduction of hyperpolarization and vasodilation along hamster feed artery. , 2000, Circulation research.

[40]  K. Frei,et al.  Occludin proteolysis and increased permeability in endothelial cells through tyrosine phosphatase inhibition. , 1999, Journal of cell science.

[41]  P. Ridker,et al.  Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men. , 1999, The American journal of cardiology.

[42]  M. Lampugnani,et al.  Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[43]  E. Vicaut,et al.  Acute modulation of albumin microvascular leakage by advanced glycation end products in microcirculation of diabetic rats in vivo. , 1999, Diabetes.

[44]  S. Russell,et al.  Aerobic exercise training can reverse age-related peripheral circulatory changes in healthy older men. , 1999, Circulation.

[45]  B. Pedersen,et al.  A high plasma concentration of TNF-alpha is associated with dementia in centenarians. , 1999, The journals of gerontology. Series A, Biological sciences and medical sciences.

[46]  A. Maio,et al.  Downregulation of connexin 43 gene expression in rat heart during inflammation. The role of tumour necrosis factor. , 1999, Cytokine.

[47]  D. Goodenough,et al.  Diverse functions of vertebrate gap junctions. , 1998, Trends in cell biology.

[48]  T Vernet,et al.  Alteration of Endothelial Cell Monolayer Integrity Triggers Resynthesis of Vascular Endothelium Cadherin* , 1998, The Journal of Biological Chemistry.

[49]  G. Paolisso,et al.  Advancing age and insulin resistance: role of plasma tumor necrosis factor-α. , 1998, American Journal of Physiology. Endocrinology and Metabolism.

[50]  R. Rolandi,et al.  Role of Advanced Glycation End Products in Aging Collagen , 1998, Gerontology.

[51]  R. Ross,et al.  Cleavage of beta-catenin and plakoglobin and shedding of VE-cadherin during endothelial apoptosis: evidence for a role for caspases and metalloproteinases. , 1998, Molecular biology of the cell.

[52]  S. Dhein Gap junction channels in the cardiovascular system: pharmacological and physiological modulation. , 1998, Trends in pharmacological sciences.

[53]  B. Ames,et al.  The free radical theory of aging matures. , 1998, Physiological reviews.

[54]  H. Jongsma,et al.  TUMOUR NECROSIS FACTOR α ALTERS THE EXPRESSION OF CONNEXIN43, CONNEXIN40, AND CONNEXIN37, IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS , 1998 .

[55]  J. Baynes,et al.  N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. , 1997, The Biochemical journal.

[56]  I H Sarelius,et al.  Direct coupling between blood flow and metabolism at the capillary level in striated muscle. , 1997, The American journal of physiology.

[57]  I. Cotgreave,et al.  Differential regulation of gap junctions by proinflammatory mediators in vitro. , 1997, The Journal of clinical investigation.

[58]  G. Jerums,et al.  Vascular hypertrophy in experimental diabetes. Role of advanced glycation end products. , 1997, The Journal of clinical investigation.

[59]  E. Schleicher,et al.  Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. , 1997, The Journal of clinical investigation.

[60]  Ignarro Lj Physiology and pathophysiology of nitric oxide. , 1996 .

[61]  R. Bucala,et al.  Prevention of cardiovascular and renal pathology of aging by the advanced glycation inhibitor aminoguanidine. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[62]  B. Geiger,et al.  The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, beta-catenin, and alpha- catenin with vascular endothelial cadherin (VE-cadherin) , 1995, The Journal of cell biology.

[63]  B. Duling,et al.  Dye tracers define differential endothelial and smooth muscle coupling patterns within the arteriolar wall. , 1995, Circulation research.

[64]  B. Duling,et al.  Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. , 1995, The American journal of physiology.

[65]  W. Mayhan Nitric oxide accounts for histamine-induced increases in macromolecular extravasation. , 1994, The American journal of physiology.

[66]  S. Segal,et al.  Cell-to-cell communication coordinates blood flow control. , 1994, Hypertension.

[67]  R. Bucala,et al.  Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[68]  E. Lakatta,et al.  Cardiovascular regulatory mechanisms in advanced age. , 1993, Physiological reviews.

[69]  K. Schechtman,et al.  Effects of Aging, Gender, and Physical Training on Peripheral Vascular Function , 1991, Circulation.

[70]  S. Albelda,et al.  Integrins and other cell adhesion molecules , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[71]  S S Segal,et al.  Propagation of vasomotor responses coordinates arteriolar resistances. , 1989, The American journal of physiology.

[72]  J. Marshall,et al.  Direct observations of muscle arterioles and venules following contraction of skeletal muscle fibres in the rat. , 1984, Journal of Physiology.

[73]  C. Sibley,et al.  The intercellular junctions of guinea-pig placental capillaries: a possible structural basis for endothelial solute permeability. , 1983, Journal of ultrastructure research.

[74]  B. Duling,et al.  Interrelations between contracting striated muscle and precapillary microvessels. , 1978, The American journal of physiology.

[75]  G. Palade,et al.  STUDIES ON INFLAMMATION , 1961, The Journal of biophysical and biochemical cytology.

[76]  N. Rummery,et al.  Australian Physiological and Pharmacological Society Symposium : Cellular and Mechanical Coupling in the Arteriolar Wall HETEROGENEITY IN THE DISTRIBUTION OF VASCULAR GAP JUNCTIONS AND CONNEXINS : IMPLICATIONS FOR FUNCTION , 2002 .

[77]  K. Yarasheski,et al.  Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[78]  H. Chung,et al.  The inflammation hypothesis of aging: molecular modulation by calorie restriction. , 2001, Annals of the New York Academy of Sciences.

[79]  M. Lampugnani,et al.  The molecular organization of endothelial junctions and their functional role in vascular morphogenesis and permeability. , 2000, The International journal of developmental biology.

[80]  E. Lakatta,et al.  Increased expression of matrix metalloproteinase-2 in the thickened intima of aged rats. , 1999, Hypertension.

[81]  Donald G Welsh,et al.  Endothelial and smooth muscle cell conduction in arterioles controlling blood flow. , 1998, American journal of physiology. Heart and circulatory physiology.

[82]  H. Jongsma,et al.  Tumour necrosis factor alpha alters the expression of connexin43, connexin40, and connexin37 in human umbilical vein endothelial cells. , 1998, Cytokine.

[83]  J. Lexell,et al.  Sarcopenia and physical performance in old age: Overview , 1997, Muscle & nerve. Supplement.

[84]  P. J. Newman,et al.  The biology of PECAM-1. , 1997, The Journal of clinical investigation.

[85]  L. Ignarro Physiology and pathophysiology of nitric oxide. , 1996, Kidney international. Supplement.

[86]  D. Lagunoff,et al.  Effect of age on mast cell granules. , 1981, International archives of allergy and applied immunology.

[87]  P. Guillausseau,et al.  Rapid Publication , 1971, Nature.