EFFECT OF ANGIOTENSIN PEPTIDES ON VASCULAR REMODELING

Cardiovascular disease, including hypertension and coronary artery disease (CAD), accounts for one in every three deaths in the United States with a direct cost estimated at $286 billion each year. Angiotensin II (Ang II), one of the biologically active peptides of the renin-angiotensin system, elicits many maladaptive effects on the cardiovascular system. Over the past two decades, numerous studies demonstrated that the other biologically active angiotensin peptide, angiotensin-(1-7) [Ang-(1-7)], counter-regulates the actions of Ang II. We demonstrated in Ang II-dependent hypertension that Ang-(1-7) prevents structural remodeling of the microcirculation independent of blood pressure. The heptapeptide hormone decreased the Ang II-induced media to lumen ratio (M/L) by 50%, perivascular fibrosis by 24% and interstitial fibrosis by 46%. These structural reductions were associated with a 32.8% decrease in connective tissue growth factor (CTGF), a 43.1% inhibition in phosphorylated Smad 2 and a 66.2% reduction in phosphorylated ERK1/2 in the arteriole wall of the cremaster muscle. Microvascular remodeling was independent of TGF-beta expression. The dual-specificity phosphatase-1 (DUSP-1) was upregulated in Ang-(1-7) treated animals with or without Ang II, suggesting that the heptapeptide prevents microvascular remodeling by dephosphorylating MAP kinase to inhibit downstream signaling pathways.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2012

Author dc:creator

• Carver, Kyle

• Angiotensin-(1-7)

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/37256

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/37256