Molecular Mechanisms of Hypertensive Nephropathy: Renoprotective Effect of Losartan through Hsp70

COSTANTINO VALERIA; GIL LORENZO ANDREA; BOCANEGRA, VICTORIA; GARRAMUÑO VALLÉS , P

Cells

MDPI, Basel, Switzerland.

Lugar: Basel; Año: 2021 vol. 10 p. 3146 - 3162

2073-4409

Abstract: Hypertensive nephrosclerosis is the second most common cause of end-stage renal diseaseafter diabetes. For years, hypertensive kidney disease has been focused on the afferent arterioles andglomeruli damage and the involvement of the renin angiotensin system (RAS). Nonetheless, in recentyears, novel evidence has demonstrated that persistent high blood pressure injures tubular cells,leading to epithelial?mesenchymal transition (EMT) and tubulointerstitial fibrosis. Injury primarilydetermined at the glomerular level by hypertension causes changes in post-glomerular peritubularcapillaries that in turn induce endothelial damage and hypoxia. Microvasculature dysfunction, byinducing hypoxic environment, triggers inflammation, EMT with epithelial cells dedifferentiationand fibrosis. Hypertensive kidney disease also includes podocyte effacement and loss, leading todisruption of the filtration barrier. This review highlights the molecular mechanisms and histologicaspects involved in the pathophysiology of hypertensive kidney disease incorporating knowledgeabout EMT and tubulointerstitial fibrosis. The role of the Hsp70 chaperone on the angiotensinII?induced EMT after angiotensin II type 1 receptor (AT1R) blockage, as a possible molecular targetfor therapeutic strategy against hypertensive renal damage is discussed.