Atherosclerotic Calcification: Wnt Is the Hint

C ardiovascular diseases remain the primary cause of death. 1 Myocardial infarction (MI), angina, and stroke take >16 million lives every year, but the underlying mechanisms by which these often-fatal cardiovascular events occur tend to escape attention.2 Atherosclerosis is the underlying pathological inflammatory vascular disease not only responsible for most MIs and strokes, but it accounts for 29% of deaths worldwide.1,3 Once believed to be a passive process, it is now understood that atherosclerosis takes an active route involving several cell types, with contributions from a multitude of organ systems, molecular mechanisms, and other pathological conditions, including, but not limited to, hypertension, hyperlipidemia, and type 2 diabetes mellitus.1,[3][4][5] Atherosclerosis is characterized by the accumulation of lipids, fibrous elements, and inflammatory cells within the vascular wall of medium and large muscular and elastic arteries.1,3,6 Atherosclerotic plaque formation leads to intimal thickening and luminal stenosis.1 Reduction of blood flow ensues, leading to ischemia of the brain, heart, and extremities and clinically manifesting as MI, angina, or stroke.The main features of atherosclerosis are endothelial dysfunction, intimal thickening, inflammation, and vascular calcification (VC).4,7,8 These processes are considered a consequence to vascular injury. 1 VC is characterized by calcium deposition in the walls of the vasculature.5 Expansion of the calcified lesion leads to thrombus formation and, if significant enough, vascular occlusion.Although the exact mechanisms for VC are unknown, there has been an increase in interest about the role Wingless (Wnt) signaling plays in disease pathogenesis.Briefly, the Wnt signaling pathway is an evolutionarily conserved pathway across kingdom Animalia and plays a crucial role in pattern formation during embryogenesis.9 The Wnt signal transduction pathway plays a crucial role in organ formation in embryonic development, cell proliferation, polarity, migration, and differentiation.10 Thus, deregulated Wnt signaling is associated with many human diseases.11 Therefore, it is justifiable to suggest that research delineating atherogenesis, with focus on the contribution of Wnt signaling in the pathogenesis of atherosclerotic calcification, is warranted. Components of the Vasculature System EndotheliumThe vascular endothelium has a multifaceted role, acting simultaneously as a permeability barrier, a nonthrombogenic surface, a regulator of vascular tone and transendothelial flow, and an inhibitor of vascular smooth muscle cell (VSMC) growth and migration.12 Under normal circumstances, endothelial cells (ECs) release an array of vasodilators and anticoagulants, such as NO and prostacyclin, which reduce platelet aggregation, monocyte and leukocyte adhesion, and VSMC proliferation.13 Under pathological conditions, ECs release factors, such as thromboxane and endothelin-1, that increase platelet aggregation, monocyte adhesion, vasoconstriction, and VSMC proliferation.Wnt signaling has been shown to be involved in EC permeability, proliferation, and survival.[14][15][16] Naturally, b-catenin binds to cadherins to stabilize adhesion of neighboring ECs.17 During cellular migration, however, b-catenin localizes in the nucleus, resulting in a loss of tissue integrity.18 Vascular Smooth Muscle CellsSmooth muscle cells of the vasculature are found as 1 of 2 possible phenotypes: the first is the contractile phenotype, the predominant form of VSMC, in the tunica media; and the second is the activated synthetic phenotype, in the tunica intima.12 The differentiated contractile VSMCs can be

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.