New dimension of statin action on apoB atherogenicity

Abstract

Newer, more effective statins are powerful agents for reducing elevated levels of low‐density lipoprotein (LDL) cholesterol and thereby lowering the risk of coronary heart disease (CHD) and related adverse events. Although LDL remains the primary target of therapy for reducing CHD risk, increased interest is focusing on apolipoprotein B (apoB)‐containing lipoprotein subfractions—particularly very‐low‐density lipoprotein (VLDL), VLDL remnants, and intermediate‐density lipoproteins (IDL)—as secondary targets of therapy. Elevated apoB is known to be an important risk factor for CHD, and dysregulation of the metabolism of apoB‐containing lipoproteins is involved in the progression of atherosclerosis. Statins reduce circulating concentrations of atherogenic apoB‐containing lipoproteins by decreasing the production of VLDL in the liver and, thus, the production of VLDL remnants and LDL. Statins also increase the clearance of these particles through upregulation of LDL receptors in the liver. Efforts to develop statins with enhanced lipid‐modifying properties are ongoing. The optimal statin would offer a high degree of inhibition of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase, a prolonged duration of action, hepatic selectivity for maximal upregulation of LDL receptors, and a low potential for drug–drug interactions. Recent studies have shown that rosuvastatin, a new agent in this class, demonstrates these qualities. Rosuvastatin is a highly effective inhibitor of HMG‐CoA reductase, is relatively nonlipophilic, has a half‐life of approximately 20 h, exhibits hepatic selectivity, has little systemic availability, and has a low potential for drug–drug interactions because of its limited degree of metabolism by the cytochrome P‐450 system. A recent double‐blind, crossover study revealed that treatment with rosuvastatin resulted in marked reductions in apoB‐containing lipoproteins in patients with type IIa or IIb dyslipidemia. By reducing the number of atherogenic lipoprotein particles, rosuvastatin decreases the atherosclerotic burden in hyperlipidemic patients at high risk for CHD and related adverse outcomes.

The blood lipid regulation of Monascus -produced monascin and ankaflavin via the suppression of low-density lipoprotein cholesterol assembly and stimulation of apolipoprotein A1 expression in the liver

“…Literature shows that lovastatin can lower apo B-100 protein level, 26 which is consistent with the results obtained for the MK group in this study. Furthermore, the experiment conducted in this study was the first time that MS and AK were observed to effectively reduce the expression of apo B-100 protein in the liver.…”

Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway

“…The proteins that were found to be significantly differentially expressed in the 2 nd phase were then validated in the 3 rd phase in 506 samples (253 Cases and 253 Controls). Although Apo B was significantly down regulated in the 2 nd phase, it was not considered for the validation phase since it is known that statin decreases the levels of Apo B2526 and most of the CAD cases in our study were consuming statins. In fact, the lower expression of ApoB that was found in both the 1 st and the 2 nd phase lends credence to our results.…”

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“…21,22 The reduction in serum cholesterol level after treatment with EGEE may be due to improved elimination of LDL from plasma by mounting LDL-receptor activity. 23 X 100 X 100…”