Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases

Low-density lipoprotein (LDL) plays a key role in the development and progression of atherosclerosis and cardiovascular disease. LDL consists of several subclasses of particles with different sizes and densities, including large buoyant (lb) and intermediate and small dense (sd) LDLs. It has been well documented that sdLDL has a greater atherogenic potential than that of other LDL subfractions and that sdLDL cholesterol (sdLDL-C) proportion is a better marker for prediction of cardiovascular disease than that of total LDL-C. Circulating sdLDL readily undergoes multiple atherogenic modifications in blood plasma, such as desialylation, glycation, and oxidation, that further increase its atherogenicity. Modified sdLDL is a potent inductor of inflammatory processes associated with cardiovascular disease. Several laboratory methods have been developed for separation of LDL subclasses, and the results obtained by different methods can not be directly compared in most cases. Recently, the development of homogeneous assays facilitated the LDL subfraction analysis making possible large clinical studies evaluating the significance of sdLDL in the development of cardiovascular disease. Further studies are needed to establish guidelines for sdLDL evaluation and correction in clinical practice

Use of Natural Products for Direct Anti-Atherosclerotic Therapy

Atherosclerosis and vascular disorders, which result from atherosclerosis, represent one of the major problems in the modern medicine and public health. Atherosclerosis is characterized by structural and functional changes of large arteries. The approaches for the treatment of atherosclerosis require at least the prevention of growth of atherosclerotic lesions and reduction in the lipid core mass, which would followed by plaque stabilization. Taken together, these approaches could theoretically result in the regression of arterial lesions. Atherosclerosis develops in the arterial wall and remains asymptomatic until ischemia of distal organs is evident. Therapy of clinical manifestations of atherosclerosis is largely aimed at reducing symptoms or affecting hemodynamic response and often does not affect the cause or course of disease, namely the atherosclerotic lesion itself. Of course, anti-atherosclerotic effects of statins revealed in many prospective clinical trials may be considered; however, statins have never been recognized as the drugs indicated just for direct treatment or prevention of atherosclerosis. They are used predominately in the course of hypolipidemic therapy, and the effects of treatment are estimated by success in reaching the target level of low density lipoprotein (LDL) cholesterol, but not the regression of atherosclerotic lesion or intimamedia thickness. The last should be considered as beneficial effect, which is mainly due to pleiotropic mechanisms of action. Atherosclerosis develops over many years, so anti-atherosclerotic therapy should be a long-term or even lifelong therapy. Tachyphylaxis, long-term toxicity and cost amongst other issues may present problems for the use of conventional medications in a long-term. Drugs based on natural products can be a good alternative

Biomarkers in Coronary Artery Bypass Surgery: Ready for Prime Time and Outcome Prediction?

Coronary artery bypass surgery (CABG) is still one of the most frequently performed surgical procedures all over the world. The results of this procedure have been constantly improved over the years with low perioperative mortality rates, with relatively low complication rates. To further improve these outstanding results, the clinicians focused their attention at biomarkers as outcome predictors. Although biological testing for disease prediction has already been discussed many times, the role of biomarkers in outcome prediction after CABG is still controversial. In this article, we reviewed the current knowledge regarding the role of genetic and dynamic biomarkers and their possible association with the occurrence of adverse clinical outcomes after CABG. We also took into consideration that the molecular pathway activation and the possible imbalance may affect hard outcomes and graft patency. We analyzed biomarkers classified in two different categories depending on their possibility to change over time: genetic markers and dynamic markers. Moreover, we evaluated these markers by dividing them, into sub-categories, such as inflammation, hemostasis, renin-angiotensin, endothelial function, and other pathways. We showed that biomarkers might be associated with unfavorable outcomes after surgery, and in some cases improved outcome prediction. However, the identification of a specific panel of biomarkers or of some algorithms including biomarkers is still in an early developmental phase. Finally, larger studies are needed to analyze broad panel of biomarkers with the specific aim to evaluate the prediction of hard outcomes and graft patency

Vasculoprotective Role of Olive Oil Compounds via Modulation of Oxidative Stress in Atherosclerosis

Existing evidence supports the significant role of oxidative stress in the endothelial injury, and there is a direct link between increased oxidative stress, and the development of endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerosis and subsequent cardiovascular disease (CVD). The overproduction of reactive oxygen species facilitates the processes, such as oxidative modification of low-density lipoproteins and phospholipids, reduction in the NOS-derived nitric oxide, and the functional disruption of high-density lipids that are profoundly involved in atherogenesis, inflammation, and thrombus formation in vascular cells. Thus, under oxidative stress conditions, endothelial dysfunction was found to be associated with the following endothelial alterations: reduced nitric oxide bioavailability, increased anticoagulant properties, increased platelet aggregation, increased expression of adhesion molecules, chemokines, and cytokines. In this review, we summarized the evidence indicating that endothelial damage triggered by oxidation can be diminished or reversed by the compounds of olive oil, a readily available antioxidant food source. Olive oil bioactive compounds exhibited a potent capability to attenuate oxidative stress and improve endothelial function through their anti-inflammatory, anti-oxidant, and anti-thrombotic properties, therefore reducing the risk and progression of atherosclerosis. Also, their molecular mechanisms of action were explored to establish the potential preventive and/or therapeutic alternatives to the pharmacological remedies available

Low density lipoprotein-induced lipid accumulation is a key phenomenon of atherogenesis at the arterial cell level

Lipid accumulation in cells of subendothelial intima and the formation of foam cells is the earliest and the most noticeable manifestation of atherosclerosis at the cellular level. Generally, the foam cell formation is the result of interaction of cell with pro-atherogenic low-density lipoprotein providing cholesterol delivery and anti-atherogenic high-density lipoprotein providing its efflux. In this review, we discuss possible mechanisms of foam cell formation, the role of intracellular lipid deposition as a trigger of atherosclerotic lesion development, current approaches to diagnostics and strategies for preventing atherosclerosis based on recent knowledge of causes of foam cell formation

Long non-coding RNA in regulation of plasticity of vascular smooth muscle cells

Phenotypic plasticity of vascular smooth muscle cells (VSMCs) is a functional property that is essential for vascular remodeling in vessel injury healing. During phenotypic switch, quiescent VSMCs loss contractile capacity but acquire ability to proliferate and migrate to the injured site where they differentiate again to the quiescent state. However, in pathological conditions such as endothelial dysfunction or atherosclerosis, phenotypic changes in arterial VSMCs become deregulated leading to elevated VSMC dedifferentiation, proliferation, excessive extracellular matrix deposits, and intimal thickening. VSMC hyperplasia is a complex mechanism that is coordinated by a network of various regulatory factors. Long non-coding (lnc)RNAs represent an important part of this regulatory network. Some of lncRNAs are involved in VSMC differentiation, apoptosis, and maintenance of VSMC quiescence, while other lncRNAs promote VSMC dedifferentiation, proliferation, and motility. In this review, we characterize these RNAs and their function in the context of possible involvement to atherosclerosis