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EFFECT OF ANGIOTENSIN PEPTIDES ON VASCULAR REMODELING

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abstract
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.
subject
Angiotensin-(1-7)
Angiotensin II
Hypertension
Restenosis
Vascular Remodeling
VSMC
contributor
Carver, Kyle (author)
Tallant, Ann (committee chair)
Metheny-Barlow, Linda (committee member)
Callahan, Michael (committee member)
Smith, Thomas (committee member)
date
2012-06-12T08:35:47Z (accessioned)
2013-06-12T08:30:11Z (available)
2012 (issued)
degree
Physiology and Pharmacology (discipline)
embargo
2013-06-12 (terms)
identifier
http://hdl.handle.net/10339/37256 (uri)
language
en (iso)
publisher
Wake Forest University
title
EFFECT OF ANGIOTENSIN PEPTIDES ON VASCULAR REMODELING
type
Dissertation

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