Switching of vascular cells towards atherogenesis, and other factors contributing to atherosclerosis: a systematic review

Abstract

Background Onset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates the changes in vasculature that contribute to switching of vascular cells towards atherogenesis, focusing mainly on ageing. Methods Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving atherogenesis, vascular homeostasis, aging, gene expression, signaling pathways, angiogenesis, vascular development, vascular cell differentiation and maintenance, vascular stem cells, endothelial and vascular smooth muscle cells. Results Atherogenesis is a complex multistep process that unfolds in a sequence. It is caused by alterations in: epigenetics and genetics, signaling pathways, cell circuitry, genome stability, heterotypic interactions between multiple cell types and pathologic alterations in vascular microenvironment. Such alterations involve pathological changes in: Shh, Wnt, NOTCH signaling pathways, TGF beta, VEGF, FGF, IGF 1, HGF, AKT/PI3K/ mTOR pathways, EGF, FOXO, CREB, PTEN, several apoptotic pathways, ET – 1, NF-κB, TNF alpha, angiopoietin, EGFR, Bcl − 2, NGF, BDNF, neurotrophins, growth factors, several signaling proteins, MAPK, IFN, TFs, NOs, serum cholesterol, LDL, ephrin, its receptor pathway, HoxA5, Klf3, Klf4, BMPs, TGFs and others. This disruption in vascular homeostasis at cellular, genetic and epigenetic level is involved in switching of the vascular cells towards atherogenesis. All these factors working in pathologic manner, contribute to the development and progression of atherosclerosis. Conclusion The development of atherosclerosis involves the switching of gene expression towards pro-atherogenic genes. This happens because of pathologic alterations in vascular homeostasis. When pathologic alterations in epigenetics, genetics, regulatory genes, microenvironment and vascular cell biology accumulate beyond a specific threshold, then the disease begins to express itself phenotypically. The process of biological ageing is one of the most significant factors in this aspect as it is also involved in the decline in homeostasis, maintenance and integrity. The process of atherogenesis unfolds sequentially (step by step) in an interconnected loop of pathologic changes in vascular biology. Such changes are involved in ‘switching’ of vascular cells towards atherosclerosis.

Fusobacterium nucleatum Accelerates Atherosclerosis via Macrophage-Driven Aberrant Proinflammatory Response and Lipid Metabolism

“…The increasing pro-atherogenic cytokines in the plaque microenvironment could contribute to the development of atherosclerosis ( Shafi, 2020 ). To examine the pro-atherogenic mediators during F. nucleatum challenge, protein levels in the aorta were detected by immunohistochemistry.…”

Porphyromonas gingivalis Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells

“…Proinflammatory cytokines IL-1β and TNF-α are significantly produced during ischemic brain damage by activated cells, such as endothelial cells [ 81 , 82 ], impairing the BBB [ 83 ]. IL-1β [ 84 ] and TNF-α [ 85 ] have been recognized as important vascular and systemic inflammatory mediators that contribute to atherogenesis. Moreover, the administration of IL-1β and TNFα induces cell death in astrocytes [ 86 ].…”

A Review of Red Yeast Rice, a Traditional Fermented Food in Japan and East Asia: Its Characteristic Ingredients and Application in the Maintenance and Improvement of Health in Lipid Metabolism and the Circulatory System

“…There has been a lot of evidence reported on the favorable actions of statins, including their HMG-CoA reductase inhibiting activity which suppresses atheroma formation in atherosclerosis [ 52 , 53 , 54 ], improving effects on blood circulation [ 55 , 56 ], and pleiotropic effects on nitric oxide (NO) production which plays a pivotal role in homeostasis of the cardiovascular system and the NO synthetase–NO pathway [ 57 , 58 , 59 ]. Effects of lovastatin on atherogenic signaling cascades [ 60 ] have also been reported [ 61 , 62 , 63 ]. There have also been similar favorable reports of red yeast rice extracts, such as upregulation of constitutive NO synthetase expression, the increase in plasma levels of nitric oxides and improvement of abnormal hemorheology in an atherosclerotic rat model induced by high-cholesterol diet feeding [ 64 ].…”