EFFECTS OF ALPHA LIPOIC ACID ON ENDOTHELIAL PROGENITOR CELLS IN 5/6 NEPHRECTOMIZED RATS
Zhang Pei-Yan, Chen Ding-Ding* and Cao Teng-Li
Abstract
Objective: Patients with chronic renal failure have high risk of
cardiovascular diseases that are closely related to impaired
angiogenesis and endothelial dysfunction. Previous researches
demonstrate that endothelial progenitor cells play key roles in
angiogenesis and re-endothelialization. We hypothesized that alpha
lipoic acid could ameliorate cardiovascular diseases in 5/6 NX rats
through affecting endothelial progenitor cells. Methods: Male
Sprague-Dawley rats were randomly divided into sham-operated
group, 5/6 nephrectomy group, Alpha lipoic acid low dose (70 mg/kg)
and high dose group (150 mg/kg). Serum creatinine and urea nitrogen
concentrations were measured after six and eight weeks respectively. Cardiac function was
detected with an invasive carotid artery catheter in conscious rats after eight weeks.
Endothelial function was assessed by pre-contracting thoracic aortic ring with phenylephrine,
followed by treatment with acetylcholine or sodium nitroprusside. Expression levels of
CD133、CD31、CD34 and KDR in both thoracic aorta and coronary artery were examined
by real-time quantitative PCR. Results: Chronic renal failure severely impaired aortic
endothelial-dependent vasodilatation and cardiac function which were ameliorated by LA.
Real-time PCR analysis confirmed that expression levels of endothelial progenitor cell
markers such as CD133、CD31、CD34 and KDR reduced in 5/6 nephrectomized rats were
noticeably increased after treatment with LA. Conclusion: These results demonstrate that LA
ameliorated endothelial function as well as cardiac function in 5/6 NX rats through affecting
endothelial progenitor cells. It suggests that LA-based therapy could provide a novel
therapeutic strategy of cardiovascular diseases.
Keywords: alpha lipoic acid; cardiovascular diseases; chronic renal failure; endothelial progenitor cells.
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