C-reactive protein levels and prevalence of chronic infections in subjects with hypoalphalipoproteinemia.

Low levels of high-density lipoprotein cholesterol (HDL-C) show a consistent relationship with the development of atherosclerosis. The underlying mechanisms are not well understood, but recent studies in subjects with primary hypoalphalipoproteinemia suggest that this could represent a proinflammatory condition. To better assess the link between HDL-C levels and C-reactive protein levels and the possible role of chronic infections as putative mediators of this relationship, we studied a population sample with nonselected causes of hypoalphalipoproteinemia. Eighty-six consecutive patients with HDL-C levels below 40 mg/dL who attend our lipid clinic and 86 control subjects with normal concentrations matched for gender, age, smoking habit, and weight were included in the study. Mean HDL-C levels were 34 +/- 3.9 and 55.4 +/- 8.8 mg/dL for subjects with hypoalphalipoproteinemia and control subjects, respectively. C-reactive protein concentrations were increased in case patients as compared with control subjects (2.13 +/- 2.0 vs 1.52 +/- 1.8 mg/L; P = .025). The prevalence of herpes simplex virus type 1, cytomegalovirus, Chlamydia pneumoniae , and Helicobacter pylori infections did not differ between the 2 groups. Although a possible confounding variable could be a degree of insulin resistance within the group of patients with low HDL-C levels, our results indicate that C-reactive protein levels are increased in subjects with nonselected hypoalphalipoproteinemia and that chronic infections do not appear to mediate this relationship.

Atorvastatin reduces the expression of cyclooxygenase-2 in a rabbit model of atherosclerosis and in cultured vascular smooth muscle cells.

Inflammation is involved in the genesis and rupture of atherosclerotic plaques. We assessed the effect of atorvastatin (ATV) on the expression of cyclooxygenase-2 (COX-2) and other proinflammatory molecules in a rabbit model of atherosclerosis. Fourteen animals underwent injury of femoral arteries and 2 weeks of atherogenic diet. Afterwards, they were randomized to receive either 5 mg/kg per day of ATV (n=8) or no treatment (NT, n=6) during 4 weeks, and were finally killed. ATV reduced lipid levels, neointimal size (0.13 (0.03-0.29) mm(2) vs 0.65 (0.14-1.81) mm(2), P=0.005) and the percentage of neointimal area positive for macrophages (1% (0-3) vs 19% (5-32), P=0.001), COX-2 (32% (23-39) vs 60% (37-81) P=0.019), interleukin-8 (IL-8) (23% (3-63) vs 63% (25-88) P=0.015), and metalloproteinase-3 (19% (12-34) vs 42% (27-93), P=0.010), without significant differences in COX-1 expression (immunohistochemistry). In situ hybridization confirmed a decreased expression of COX-2 mRNA (22% (5-40) vs 43% (34-59) P=0.038). The activity of nuclear factor-kappaB, which controls many proinflammatory genes including COX-2, was reduced in atherosclerotic lesions (3538 (2663-5094) vs 8696 (5429-11312)) positive nuclei per mm(2), P=0.001) and circulating mononuclear cells (2966 vs 17130 arbitrary units). In cultured vascular smooth muscle cells, ATV reduced the expression of COX-2 mRNA induced by IL-1beta and TNF-alpha without affecting COX-1 expression. In conclusion, ATV, besides decreasing a number of inflammatory mediators in the atherosclerotic lesion, significantly downregulates COX-2 both in vivo and in vitro. These anti-inflammatory actions could partially account for the reduction of acute coronary events achieved by statins.