The genetic basis for altered blood vessel function in disease: large artery stiffening.
The progressive stiffening of the large arteries in humans that occurs during aging constitutes a potential risk factor for increased cardiovascular morbidity and mortality, and is accompanied by an elevation in systolic blood pressure and pulse pressure. While the underlying basis for these changes remains to be fully elucidated, factors that are able to influence the structure and composition of the extracellular matrix and the way it interacts with arterial smooth muscle cells could profoundly affect the properties of the large arteries. Thus, while age and sex represent important factors contributing to large artery stiffening, the variation in growth-stimulating factors and those that modulate extracellular production and homeostasis are also being increasingly recognized to play a key role in the process. Therefore, elucidating the contribution that genetic variation makes to large artery stiffening could ultimately provide the basis for clinical strategies designed to regulate the process for therapeutic benefit.
Agrotis
Alex
A
The Cell Biology Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia. alex.agrotis@baker.edu.au
D001158:Arteries / Q000378:metabolism / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D024042:Collagen Type I / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D004548:Elasticity; D004549:Elastin / Q000235:genetics; D016232:Endothelins / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D000071837:Fibrillins; D019204:GTP-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics; D011110:Polymorphism, Genetic; D017466:Receptors, Endothelin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics
D024042:Collagen Type I; D016232:Endothelins; D016326:Extracellular Matrix Proteins; D000071837:Fibrillins; D008840:Microfilament Proteins; D017466:Receptors, Endothelin; D004549:Elastin; D019001:Nitric Oxide Synthase; D019405:Cytochrome P-450 CYP11B2; D053505:Matrix Metalloproteinases, Secreted; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D019204:GTP-Binding Proteins