Despite being the most common treatment strategy in the management of atherosclerosis and subsequent cardiovascular disease, classical statin therapy has certain disadvantages, including numerous side effects. In addition, a regimen with daily administration of the drug is hard to comply with. Thus, there is a need for modern and more efficient therapeutic strategies in CVD treatment. There is extensive evidence indicating that PCSK9 promotes atherogenesis through a variety of mechanisms. Thus, new treatment methods can be developed that prevent or alleviate atherosclerotic cardiovascular disease by targeting PCSK9. Comprehensive understanding of its atherogenic properties is a necessary precondition for the establishment of new therapeutic strategies. In this review, we will summarize the available data on the role of PCSK9 in the development and progression of atherosclerosis. In the last section, we will consider existing PCSK9 inhibitors.
Pericytes are perivascular multipotent cells wrapping microvascular capillaries, where they support vasculature functioning, participate in tissue regeneration, and regulate blood flow. However, recent evidence suggests that in addition to traditionally credited structural function, pericytes also manifest immune properties. In this review, we summarise recent data regarding pericytes’ response to different pro-inflammatory stimuli and their involvement in innate immune responses through expression of pattern-recognition receptors. Moreover, pericytes express various adhesion molecules, thus regulating trafficking of immune cells across vessel walls. Additionally, the role of pericytes in modulation of adaptive immunity is discussed. Finally, recent reports have suggested that the interaction with cancer cells evokes immunosuppression function in pericytes, thus facilitating immune evasion and facilitating cancer proliferation and metastasis. However, such complex and multi-faceted cross-talks of pericytes with immune cells also suggest a number of potential pericyte-based therapeutic methods and techniques for cancer immunotherapy and treatment of autoimmune and auto-inflammatory disorders.
Pericytes are multipotent mesenchymal stromal cells playing an active role in angiogenesis, vessel stabilisation, maturation, remodelling, blood flow regulation and are able to trans-differentiate into other cells of the mesenchymal lineage. In this review, we summarised recent data demonstrating that pericytes play a key role in the pathogenesis and development of atherosclerosis (AS). Pericytes are involved in lipid accumulation, inflammation, growth, and vascularization of the atherosclerotic plaque. Decreased pericyte coverage, endothelial and pericyte dysfunction is associated with intraplaque angiogenesis and haemorrhage, calcification and cholesterol clefts deposition. At the same time, pericytes can be used as a novel therapeutic target to promote vessel maturity and stability, thus reducing plaque vulnerability. Finally, we discuss recent studies exploring effective AS treatments with pericyte-mediated anti-atherosclerotic, anti-inflammatory and anti-apoptotic effects.
Since the end of the 20th century, it has been clear that atherosclerosis is an inflammatory disease. However, the main triggering mechanism of the inflammatory process in the vascular walls is still unclear. To date, many different hypotheses have been put forward to explain the causes of atherogenesis, and all of them are supported by strong evidence. Among the main causes of atherosclerosis, which underlies these hypotheses, the following can be mentioned: lipoprotein modification, oxidative transformation, shear stress, endothelial dysfunction, free radicals’ action, homocysteinemia, diabetes mellitus, and decreased nitric oxide level. One of the latest hypotheses concerns the infectious nature of atherogenesis. The currently available data indicate that pathogen-associated molecular patterns from bacteria or viruses may be an etiological factor in atherosclerosis. This paper is devoted to the analysis of existing hypotheses for atherogenesis triggering, and special attention is paid to the contribution of bacterial and viral infections to the pathogenesis of atherosclerosis and cardiovascular disease.
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