Item Details

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