Cholesterol reduction reduces ischaemic cardiovascular morbidity and mortality in the asymptomatic healthy population as well as in those with known coronary artery disease. Angiographic studies have also demonstrated regression of atherosclerotic plaques as well as retardation of new atheroma formation with such therapy. Yet, there is a consistent inability to reduce overall mortality in cholesterol-lowering drug trials. An excess of suicide, homicide and violence has been attributed to cholesterol reduction interfering with membrane lipids and receptors, leading to aggressive behaviour. The risk and benefits of cholesterol reduction must thus be weighed in the individual patient; it is more useful in those with known coronary artery disease who are at high risk of subsequent ischaemic cardiovascular events.
Cardiovascular disease (CVD) has been the main cause of mortality and an important cause of morbidity in Malaysia for several years. To reduce global cardiovascular (CV) risk in the population, primary preventive strategies need to be implemented. Hypercholesterolaemia is one of the major risk factors for CVD. This paper is an expert review on the management of hypercholesterolemia focusing on high and very high risk individuals. In low and Intermediate risk individuals, therapeutic lifestyle changes (TLC) and a healthy lifestyle alone may suffice. In high and very high risk individuals, drug therapy in conjunction with TLC are necessary to achieve the target LDL-C levels which have been shown to slow down progression and sometimes even result in regression of atherosclerotic plaques. Statins are first-line drugs because they have been shown in numerous randomized controlled trials to be effective in reducing CV events and to be safe. In some high risk individuals, despite maximally tolerated statin therapy, target Low Density Lipoprotein Cholesterol (LDL-C) levels are not achieved. These include those with familial hypercholesterolaemia and statin intolerance. This paper discusses non-statin therapies, such as ezetimibe and the newer Proprotein convertase subtilisin/kexin type 9 Inhibitors (PCSK9-i).
Fifteen strains of Lactobacillus and Bifidobacterium were screened based on their ability to adhere to hydrocarbons via the determination of cellular hydrophobicity. Lactobacillus acidophilus ATCC 314, L. acidophilus FTCC 0291, Lactobacillus bulgaricus FTCC 0411, L. bulgaricus FTDC 1311, and L. casei ATCC 393 showed greater hydrophobicity and, thus, were selected for examination of cholesterol-removal properties. All selected strains showed changes in cellular fatty acid compositions, especially total fatty acids and saturated and unsaturated fatty acids in the presence of cholesterol compared with those grown in the absence of cholesterol. In addition, we found that cells grown in media containing cholesterol were more resistant to sonication and enzymatic lysis compared with those grown without cholesterol. We further evaluated the location of the incorporated cholesterol via the insertion of fluorescence probes into the cellular membrane. In general, enrichment of cholesterol was found in the regions of the phospholipid tails, upper phospholipids, and polar heads of the cellular membrane phospholipid bilayer. Our results also showed that lactobacilli were able to reduce cholesterol via conversion of cholesterol to coprostanol, aided by the ability of strains to produce cholesterol reductase. Our results provided experimental evidence to strengthen the hypothesis that probiotics could remove cholesterol via the incorporation of cholesterol into the cellular membrane and conversion of cholesterol to coprostanol. The strains studied may be potential health adjunct cultures in fermented dairy products with possible in vivo hypocholesterolemic effects.
This study assessed the cholesterol lowering effect of Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 using adult zebrafish. Animals were fed with a high cholesterol diet (HCD) with/without LAB for seven weeks. Serum and liver cholesterol was quantified using colorimetric and dye staining methods. Expressions of npc1l1 and abca1 in the liver and intestine and appa in the brain were quantified using RT-PCR. Serum and liver cholesterol was significantly lowered in LAB4- and LAB12-fed zebrafish (≤64% and ≤71%, respectively), with reduced liver cholesterol deposition. The cholesterol lowering effect was accompanied by down-regulation of npc1l1 in intestines (≤28.7%), up-regulation of abca1 in the liver (≥30.5%) and down-regulation of appa in the brain (≤24.5%). A moderately strong positive Pearson correlation (r = 0.617, p < 0.01) was found between appa and serum cholesterol. LAB-fed zebrafish exhibited improved spatial learning and memory. LAB4 and LAB12 can be potentially used in preventing hypercholesterolaemia and Alzheimer's diseases.