RGD Reference Report - Effects of atorvastatin on angiogenesis in hindlimb ischemia and endothelial progenitor cell formation in rats.

General

Effects of atorvastatin on angiogenesis in hindlimb ischemia and endothelial progenitor cell formation in rats.
Authors:	Matsumura, M Fukuda, N Kobayashi, N Umezawa, H Takasaka, A Matsumoto, T Yao, EH Ueno, T Negishi, N
Citation:	Matsumura M, etal., J Atheroscler Thromb. 2009 Aug;16(4):319-26. Epub 2009 Aug 11.
RGD ID:	2313934
Pubmed:	PMID:19672036 (View Abstract at PubMed)
AIM: To investigate the mechanisms underlying the pro-angiogenic effects of statin, the effects of atorvastatin were investigated on the expression of angiogenic factors in ischemic hindlimbs of rats. The function and number of endothelial progenitor cells (EPCs) were investigated in hypertensive rats. METHODS: Hindlimb ischemia rats were administered 10 or 30 mg/kg/day atorvastatin orally for 2 weeks. Angiogenesis was evaluated by a laser Doppler and by Isolectin-B4 immunostaining. The expressions of VEGF, IL-8, angiopoietin (Ang)-1, Ang-2, eNOS, and hemoxidase (HO)-1 were evaluated by Western blotting and immunohistochemistry. Spontaneously hypertensive rats (SHR) were administered 10 mg/kg/day atorvastatin. EPC function was evaluated by colony formation and migration. The EPC number was evaluated by CD34-positive cells. RESULTS: A lowdose of atorvastatin, but not a highdose, significantly increased regional blood flow. Atorvastatin significantly increased the expressions of VEGF, IL-8, Ang-1, Ang-2, eNOS, and HO-1 proteins in ischemic hindlimbs. Atorvastatin significantly increased the number and colony formation of EPCs and decreased oxidation in mononuclear cells from SHR. CONCLUSION: Atorvastatin strongly induced angiogenesis with increases in angiogenic cytokines, HO-1 and EPC numbers. Statins are thus considered potertial agents for therapeutic angiogenesis.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
ischemia		ISO	Angpt2 (Rattus norvegicus)	2313934; 2313934		RGD
ischemia		IDA		2313934		RGD

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
response to organic cyclic compound		IEP		2313934	atorvastatin	RGD

Objects Annotated

Genes (Rattus norvegicus)

Angpt2 (angiopoietin 2)

Genes (Mus musculus)

Angpt2 (angiopoietin 2)

Genes (Homo sapiens)

ANGPT2 (angiopoietin 2)

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Effects of atorvastatin on angiogenesis in hindlimb ischemia and endothelial progenitor cell formation in rats.