Recruitable ACE and tissue repair in the infarcted heart.
Constitutive angiotensin-converting enzyme (ACE) is bound to endothelial cells where it serves to regulate circulating concentrations of angiotensin II (Ang II) that normally contribute to circulatory homeostasis. Recruitable ACE, bound to macrophage and myofibroblast cell membrane, regulates local concentrations of Ang II involved in tissue repair. De novo generation of Ang II modulates expression of TGF-beta1 whose autocrine/paracrine properties regulate collagen turnover at sites of fibrous tissue formation that appear in response to various forms of injury in diverse tissues. Persistent myofibroblasts and their ACE activity at the infarct site contribute to a sustained metabolic activity that can account for a progressive fibrosis at, and remote to, sites of myocardial infarction. Activation of the circulating renin-angiotensin-aldosterone system with sustained elevations in plasma Ang II and aldosterone induce a pro-inflammatory vascular phenotype of small arteries and arterioles. This further promotes the appearance of recruitable ACE bound to macrophages and myofibroblasts involved in vascular remodelling. Locally produced Ang II from these vascular sites leads to perivascular fibrosis of intramural coronary vasculature of non-infarcted myocardium. At these sites, remote to the infarct, such adverse structural remodelling by fibrous tissue eventuates in ICM, a major aetiologic factor involved in the appearance of chronic cardiac failure and contributes to its progressive nature.
Weber
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Sun
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D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1; D012016:Reference Values; D014945:Wound Healing / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A