Comparative proteomic analysis in microdissected renal vessels from hypertensive SHR and WKY normotensive rats
Systemic hypertension leads to renal damage known as hypertensive nephrosclerosis without obvious clinical symptoms in the initial stages and it has a profound impact on the renal vascular physiology. Despite its major role in End Stage Renal Disease, many aspects of hypertensive nephrosclerosis remain unknown. In order to elucidate the biological pathways and macromolecules deregulated by hypertension, renal vessels were obtained by Laser Capture Microdissection (LCM) from Spontaneously Hypertensive Rats (SHR) and age-matched controls (20 weeks). Proteomic analysis was performed aiming to detect molecular alterations associated with hypertension at the renal vessels before the onset of vascular damage. This analysis identified 688 proteins, of which 58 were differentially expressed (15 up-regulated and 43 down-regulated) in SHR. Many of these proteins are involved in vascular tone regulation by modulating the activity of endothelial Nitric Oxide Synthase (eNOS) (Xaa-Pro aminopeptidase 1 (XPP1), N(G) N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1), Dehydropteridine reductase (DHPR)) or in blood pressure control by regulating the renin-angiotensin system (Glutamyl aminopeptidase/Aminopeptidase A (AMPE), Aminopeptidase N (AMPN)). Moreover, pathway enrichment analysis revealed that the eNOS activation pathway is deregulated only in SHR. Our study demonstrates that hypertension causes early proteomic changes in the renal vessels of SHR. These changes are relevant to vascular tone regulation and consequently may be involved in the development of vascular damage and hypertensive nephrosclerosis. Further validation and interference studies to investigate potential therapeutic impact of these findings are warranted.