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Agnes B Fogo

Publications and source records attributed to Agnes B Fogo.

76 records · Page 5Linked to original sources
PubMed2002

The renin-angiotensin-aldosterone system and fibrinolysis in progressive renal disease.

Renal glomerular and interstitial fibrosis is widely viewed as the final common pathway to renal failure, regardless of the initiating injury. Similarly, the renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of renal disease. This review explores the hypothesis that the RAAS causes injury and fibrosis, in part, through effects on plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of plasminogen activators in vivo. PAI-1, by inhibiting the production of plasmin from plasminogen, tips the balance in favor of extracellular matrix accumulation and promotes fibrosis. Interruption of the RAAS decreases both PAI-1 expression and fibrosis in animal models. These findings have implications for the clinical management of renal disease.

Disease Progression↗
PubMed2002

Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis.

We examined the in vivo function of the angiotensin II type 1 receptor (Agtr1) on macrophages in renal fibrosis. Fourteen days after the induction of unilateral ureteral obstruction (UUO), wild-type mice reconstituted with marrow lacking the Agtr1 gene (Agtr1(-/-)) developed more severe interstitial fibrosis with fewer interstitial macrophages than those in mice reconstituted with Agtr1(+/+) marrow. These differences were not observed at day 5 of UUO. The expression of profibrotic genes - including TGF-beta1, alpha1(I) collagen, and alpha1(III) collagen - was substantially higher in the obstructed kidneys of mice with Agtr1(-/-) marrow than in those with Agtr1(+/+) marrow at day 14 but not at day 5 of UUO. Mice with Agtr1(-/-) marrow were characterized by reduced numbers of peripheral-blood monocytes and macrophage progenitors in bone marrow. In vivo assays revealed a significantly impaired phagocytic capability in Agtr1(-/-) macrophages. In vivo treatment of Agtr1(+/+) mice with losartan reduced phagocytic capability of Agtr1(+/+) macrophages to a level comparable to that of Agtr1(-/-) macrophages. Thus, during urinary tract obstruction, the Agtr1 on bone marrow-derived macrophages functions to preserve the renal parenchymal architecture, and this function depends in part on its modulatory effect on phagocytosis.

Animals↗
PubMedDate not supplied

Aldosterone and PAI-1: implications for renal injury.

Aldosterone modulates cardiovascular and renal injury and fibrosis in animal models. This review explores the hypothesis that aldosterone causes injury and fibrosis, in part, through effects on plasminogen activator inhibitor-1, the major physiological inhibitor of plasminogen activators in vivo. Aldosterone interacts with angiotensin II to increase plasminogen activator inhibitor-1 expression in vitro and in vivo. Plasminogen activator inhibitor-1, by inhibiting the production of plasmin from plasminogen, tips the balance in favor of extracellular matrix accumulation and promotes fibrosis. Aldosterone receptor antagonism decreases both PAI-1 expression and fibrosis in animal models. These findings have implications for the clinical management of cardiovascular and renal disease.

Aldosterone↗