Lipid accumulation in the arterial wall is a crucial event in the development of atherosclerotic lesions. Circulating low-density lipoprotein (LDL) is the major source of lipids that accumulate in the atherosclerotic plaques. It was discovered that not all LDL is atherogenic. In the blood plasma of atherosclerotic patients, LDL particles are the subject of multiple enzymatic and non-enzymatic modifications that determine their atherogenicity. Desialylation is the primary and the most important atherogenic LDL modification followed by a cascade of other modifications that also increase blood atherogenicity. The enzyme trans-sialidase is responsible for the desialylation of LDL, therefore, its activity plays an important role in atherosclerosis development. Moreover, circulating modified LDL is associated with immune complexes that also have a strong atherogenic potential. Moreover, it was shown that antibodies to modified LDL are also atherogenic. The properties of modified LDL were described, and the strong evidence indicating that it is capable of inducing intracellular accumulation of lipids was presented. The accumulated evidence indicated that the molecular properties of modified LDL, including LDL-containing immune complexes can serve as the prognostic/diagnostic biomarkers and molecular targets for the development of anti-atherosclerotic drugs.

Atherosclerosis is a complex multifactorial disease that, despite advances in lifestyle management and drug therapy, remains to be the major cause of high morbidity and mortality rates from cardiovascular diseases (CVDs) in industrialized countries. Therefore, there is a great need in reliable diagnostic/prognostic biomarkers and effective treatment alternatives to reduce its burden. It was established that microRNAs (miRNAs/miRs), a class of non-coding single-stranded RNA molecules, can regulate the expression of genes at the post-transcriptional level and, accordingly, coordinate the cellular protein expression. Thus, they are involved not only in cell-specific physiological functions but also in the cellular and molecular mechanisms of human pathologies, including atherosclerosis. MiRNAs may be significant in the dysregulation that affects endothelial integrity, the function of vascular smooth muscle and inflammatory cells, and cellular cholesterol homeostasis that drives the initiation and growth of an atherosclerotic plaque. Besides, distinct expression patterns of several miRNAs are attributed to atherosclerotic and cardiovascular patients. In this article, the evidence indicating the multiple critical roles of miRNAs and their relevant molecular mechanisms related to atherosclerosis development and progression was reviewed. Moreover, the effects of miRNAs on atherosclerosis enabled to exploit them as novel diagnostic biomarkers and therapeutic targets that may lead to better management of atherosclerosis and CVDs.

Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed. Int. J. Mol. Sci. 2020, 21, 2992 2 of 26 by the low and oscillatory endothelial shear stress [3]. According to the current understanding, lesion development involves lipid accumulation in the arterial intima, resulting in foam cell formation, a local inflammatory response, and migration and proliferation of several cell types, including macrophages, smooth muscle cells (SMCs), lymphocytes, neutrophils, and dendritic cells that play a pivotal role in its progression. Lipid accumulation is a key event in the formation of the atherosclerotic lesion, and it is determined by different classes of lipoproteins [4]. Atherosclerotic plaque tends to develop early in life [5], progressing with age; however, the progression rate is not completely predictable and varies among individuals. In general, it undergoes a prolonged asymptomatic phase (lasting many years or several decades) until the manifestation of the first clinical symptoms often at the later stages of atherosclerosis. The mechanisms of plaque progression encompass SMC apoptosis, matrix synthesis, angiogenesis, arterial remodeling, fibrous cap rupture, and thrombosis, followed by necrosis and calcification. The most acute cardiovascular events are triggered by the rupture; erosion; or, the least common, calcified nodule, the vulnerable plaque phenotypes, followed by coronary thrombosis. Ruptured lesions are responsible for the majority (73%) of all ACSs [6]. In addition, the underlying mechanism of sudden coronary death from thrombi was found from plaque erosions, in 30%-35% of cases, and rarely from calcified nodules, in 2%-7% of cases [7].The biological features of two major classes of high-risk (vulnerable) plaques, such as rupture-pron...

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in developed countries predominantly affecting the elderly population therefore posing a large economic burden. It is a gradually progressive condition ranging from mild valve calcification and thickening, without the hemodynamic obstruction, to severe calcification impairing leaflet motion, known as aortic stenosis (AS). The progression of CAVD occurs over many years, and it is extremely variable among individuals. It is also associated with an increased risk of coronary events and mortality. The recent insights into the CAVD pathophysiology included an important role of sex. Accumulating evidence suggests that, in patients with CAVD, sex can determine important differences in the relationship between valvular calcification process, fibrosis, and aortic stenosis hemodynamic severity between men and women. Consequently, it has implications on the development of different valvular phenotypes, left ventricular hypertrophy, and cardiovascular outcomes in men and women. Along these lines, taking into account the sex-related differences in diagnosis, prognosis, and treatment outcomes is of profound importance. In this review, the sex-related differences in patients with CAVD, in terms of pathobiology, clinical phenotypes, and outcomes were discussed.

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.