Apoptosis1

Atherosclerosis involves the progressive build-up of an atherosclerotic plaque in the arteries, a diseased structure consisting of cholesterol, fatty substances, immune cells, smooth muscle cells, and connective tissue. Apoptosis contributes to various stages of atherosclerosis, and its effects can influence plaque development, stability, and progression. Dysfunction of endothelial cells is an early initiating event in atherosclerosis. Endothelial cell apoptosis is one element of such dysfunction and is triggered by factors including oxidative stress, inflammation, and disturbed blood flow patterns. Apoptotic endothelial cells release pro-inflammatory signals, such as cytokines, chemokines, and danger-associated molecular patterns (DAMPs). The apoptotic endothelial cells also activate adhesion molecules on their surface, such as selectins and integrins which interact with complementary molecules on circulating monocytes, facilitating their adhesion to the endothelial cells. Monocytes, adhering to the endothelial cells via endothelial E- and P-Selectins, together with ICAM-1 and V-CAM-1, then migrate across the endothelial barrier in a process called diapedesis. Once within the arterial intima, some of these monocytes differentiate into macrophages. Macrophages that have infiltrated the arterial intima become activated in response to the pro-inflammatory environment and secrete cytokines and chemokines, amplifying the inflammatory response. Thus, endothelial cell apoptosis disrupts the protective barrier of the inner arterial lining, allowing lipids and immune cells to accumulate in the vessel wall. Macrophages are key immune cells that infiltrate the plaque, taking up oxidized lipids and becoming foam cells. Foam cells can also undergo apoptosis within the atherosclerotic plaque because of lipid overload and stress, in addition to other signals associated with inflammation. Foam cells are frequently unable to handle the excess cholesterol and other lipids they have taken up, leading to ER stress and oxidative damage, ultimately triggering apoptosis. Foam cells can also express death receptors on their surface, such as Fas receptor (CD95) and tumour necrosis factor receptor (TNFR), with binding of their ligands, present in the inflammatory plaque environment, triggering their apoptosis. Smooth muscle cells (SMCs) are a major component of the arterial wall and are normally involved in maintaining vascular structure and function. In the later stages of plaque development however, they migrate from the media to the intima of the arterial wall and contribute to the formation of fibrous caps overlying the lipid-rich atherosclerotic core. However, excessive SMC apoptosis can weaken the fibrous cap, making it more prone to rupture. Chronic inflammation within the atherosclerotic plaque can lead to the release of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) which can induce apoptotic signalling pathways in SMCs, contributing to their death. In addition, Fas ligand (FasL), a death receptor ligand that can induce apoptosis when it binds to its receptor, Fas (also known as CD95), can be upregulated on SMCs by inflammatory conditions within the plaque, leading to Fas-mediated apoptosis of SMCs. Finally, some factors, such as Bcl-2 family proteins, with anti-apoptotic roles help maintain cell survival within the plaque. However, inflammatory cytokines, such as TNF-α and IL-1, can induce the expression of additional pro-apoptotic Bcl-2 family members, thereby promoting apoptosis. We offer a wide product range of research tools for studying apoptosis, including pan-AKT antibodies, TRAIL antibodies, IGFBP3 antibodies, IGFBP3 ELISA Kits, and Angiotensinogen ELISA Kits. Explore our full apoptosis product range below and discover more, for less.