Elevated plasma endothelin-1 levels in sickle cell anemia: relationships to oxygen saturation and left ventricular hypertrophy.

Endothelin-1 (Et-1) is a vasoconstrictor produced by endothelial and vascular smooth muscle cells in response to hypoxia, which induces hypertrophy in cultured cardiac myocytes. We measured plasma Et-1 levels and left ventricular dimensions in 13 patients with sickle cell anemia (SCD) and in 12 African-American controls ages 16-29 years. Endothelin-1 concentrations are significantly higher in SCD subjects than controls (10.6 +/- 1.9 vs. 3.0 +/- 1.3 pmol/L). There was a negative correlation between oxygen saturation and Et-1 levels in SCD patients (r = -0.71, P = 0.01). SCD subjects have more dilated and hypertrophied hearts corrected for body surface area than controls as evidenced by significant increases in left ventricular end diastolic dimension (31 +/- 0.8 vs. 24 +/- 0.9 mm/m2, P < 0.001), left ventricular end systolic dimension (20 +/- 0.9 vs. 16 +/- 0.8 mm/m2, P = 0.002), left ventricular posterior wall thickness (5.0 +/- 0.1 vs. 4.0 +/- 0.1 mm/m2, P < 0.001), and left ventricular mass (125 +/- 7.2 vs. 69 +/- 5.1 g/m2, P < 0.001). The index of left ventricular function, the shortening fraction, was not different between groups (34 +/- 1.2% in SCD vs. 35 +/- 1.5% in controls). The correlation between left ventricular mass and levels of Et-1 in SCD subjects was not significant (r = 0.47, P = 0.121).

Obese pigs fed a high cholesterol diet from birth to 2 months are less susceptible than lean pigs to atherosclerosis.

Dietary cholesterol in infancy may alter cholesterol metabolism and the propensity to develop atherosclerosis. This study examined the effects of a 1% cholesterol diet (HC) vs. a no-cholesterol diet (NC) during the first 2 mo of life on pigs selectively bred for leanness or obesity. Three lean and three obese pigs received the no-cholesterol diet, and four lean and four obese pigs received the 1% cholesterol diet from d 1. Lean and obese pigs fed the no-cholesterol diet showed no increase in serum lipid concentrations, nor did they develop atherosclerosis. Obese pigs fed the 1% cholesterol diet developed significantly higher serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) at 35 d than lean pigs fed the 1% cholesterol diet. By d 55, only HDL-C remained significantly higher in the obese pigs, resulting in a higher (P < 0.1) TC/HDL-C ratio in the lean pigs. Atherosclerotic plaque formation in the aorta was more extensive in the lean pigs. Cholesterol synthesis measured in vivo and at termination was equally suppressed in lean and obese pigs fed the 1% cholesterol compared with pigs fed the no-cholesterol diet. We conclude that genetic differences in the response of these lean and obese pigs to a high cholesterol diet render obese pigs less susceptible to atherosclerosis despite higher serum TC concentrations. The persistent elevation of HDL-C in obese pigs is the most likely mechanism of protection.