Fibroblasts co-cultured with ecKO endothelial cells showed decreased collagen production, decreased insulin-like growth factor (IGF)-1/Akt/mTOR signaling, and enhanced autophagic activation. Fibroblasts, as a source of collagen in myocardium and vasculature, may play a role in the decrease in collagen deposition. Cardiovascular hypotrophy likely develops with aging, since no significant changes were observed in 2-month-old ecKO mice. Collagen was decreased in the LV myocardial interstitium and perivascularly in coronary arteries and aorta. The LV presented decreased diastolic function, and mesenteric arteries showed decreased stiffness. In 16 to 18-month-old ecKO mice, the left ventricle (LV) mass, media cross-sectional area of aorta and coronary arteries, and media-to-lumen ratio of mesenteric arteries were decreased.
In order to uncover the function of PC5/6 in the cardiovascular system, the effect of ecKO was studied in aging mice.
Because lethality at birth of mice lacking PC5/6 precluded elucidation of its function in the adult, we generated mice in which the gene of PC5/6 (pcsk5) is specifically inactivated in endothelial cells (ecKO), which are viable and do not exhibit overt abnormalities. Several studies suggest a role for PC5/6 in cardiovascular disease.
Proprotein convertase (PC) 5/6 belongs to a family of secretory proteases involved in proprotein proteolysis.
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