Atherosclerosis is the growth of fatty lesions in blood vessel walls, leading eventually to a rupture and blockage to cause a heart attack or stroke, and along the way causing narrowing of blood vessels sufficient to lead to heart failure and dysfunction elsewhere in the body as the supply of blood to tissues is reduced. Today's paper on this topic is a little disorganized, something of a random assembly of thoughts on mechanisms relevant to the development of atherosclerosis. Atherosclerosis is the single largest cause of human mortality, and attempts to treat contributing mechanisms have so far not stopped it from being the single largest cause of human mortality. So perhaps it is something that we should all be putting more thought into, and broadening the range of development programs in an attempt to produce more meaningful therapies.
Atherosclerosis is chronic arterial inflammation caused by both conventional and unconventional risk factors that result in plaque development in the vascular intima. Inflammation starts with the activation of NLRP3 inflammasomes, which results in the production of proinflammatory cytokines IL-1 and IL-18, acting via the autocrine, paracrine, or endocrine pathways. IL-1 has been demonstrated to promote its own gene expression in a variety of cell types through an amplification loop known as autoinduction. IL-1 increases endothelial dysfunction, leukocyte-endothelial cell adhesion, procoagulant activity, and neutrophil recruitment, all of which contribute to atherogenesis and plaque ruptures.
Aging is one of the strongest risk factors for atherosclerosis which increases the morbidity and mortality of patients. Understanding the mechanisms of the age-related increase in atherosclerotic diseases can better guide prevention and therapy in this risk group, since it is unclear whether aging itself increases the susceptibility to atherosclerotic diseases and their severity. In this review, we present two main areas in which aging promotes atherosclerosis. The first group of factors is those outside of the vascular system, such as the impact of age on the clonal hematopoiesis of indeterminate potential (CHIP) differentiation of hematopoietic cells in the myeloid cell lineages. The second group of factors is the vascular intrinsic ones, such as the effect of aging on vascular bioenergetics due to impairment of mitochondrial function, mitophagy (removal of damaged mitochondria), and an impact on inflammation in vessels. In addition, mitochondrial DNA damage, which is an early event of atherogenesis in apolipoprotein deficient (ApoE) mice, can result in mitochondrial dysfunction, leading to proatherogenic processes such as inflammation and apoptosis.
The vascular endothelium, as an integral component of the cardiovascular system intimately interfacing with the blood, plays a crucial role in maintaining systemic homeostasis. It acts as a lining of the cardiovascular system, forming a particular barrier to various molecules. It assumes multifaceted functions within the human body, being intricately responsive to a myriad of external stimuli present in the surrounding environment. The vascular endothelium plays a regulatory role in vascular muscle contraction, relaxation, smooth muscle proliferation, and the expression of adhesion molecules or chemotactic factors. These factors are responsible for the adhesion, activation, or migration of inflammatory cells, as well as platelet adhesion and aggregation. Additionally, the vascular endothelium influences the coagulation and fibrinolysis processes. Disruption of these processes underpins the mechanism of atherosclerosis of the blood vessels.