ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model

<p>Abstract</p> <p>Background</p> <p>We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE^-/-) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.</p> <p>Methods</p> <p>Thickening of the aortic valve leaflets in apoE^-/-mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.</p> <p>Results</p> <p>Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).</p> <p>Conclusion</p> <p>Moderate uremia causes thickening of the aortic valves in apoE^-/-mice, which can be attenuated by ACE inhibition. The nephrectomized apoE^-/-mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.</p

Hyperglycemia and Insulin Resistance and the Risk of BPH/LUTS: an Update of Recent Literature

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are highly prevalent in older men and represent a substantial challenge to public health. Increasing epidemiologic evidence suggests that diabetes and associated hyperglycemia and insulin resistance significantly increase the risks of BPH and LUTS. Plausible pathophysiologic mechanisms to explain these associations include increased sympathetic tone, stimulation of prostate growth by insulin and related trophic factors, alterations in sex steroid hormone expression, and induction of systemic inflammation and oxidative stress. This article presents a comprehensive update of the current understanding of clinical and epidemiologic research on diabetes and BPH/LUTS, describes hypothesized pathophysiologic mechanisms linking these conditions, and recommends future directions for research