Figure 2.

Overview of potential mechanisms that inhibit cell death in atherosclerosis. (A) Caspases are key effector molecules during apoptosis. Synthetic peptide inhibitors such as z-VAD-fmk are efficient in blocking apoptotic cell death in atherosclerotic plaques. However, inhibition of the classical caspase-dependent apoptotic pathway by z-VAD-fmk may induce autophagy and necrotic cell death. (B) A number of proapoptotic factors have been identified that contribute to apoptosis in atherosclerotic plaques. Examples include oxidative damage (through formation of ROS and oxLDL), endoplasmic reticulum (ER) stress and the release of pro-inflammatory cytokines such as TNFα. These apoptotic stimuli can be tackled by antioxidants, chemical chaperones or TNFα blocking agents respectively. (C) Apoptosis in atherosclerotic plaques is associated with the progressive accumulation of macrophages (MΦ) which may express a variety of cell death stimuli. Dietary lipid lowering leads to a substantial loss of macrophages. Also statins help, even though hydrophilic and hydrophobic statins may have differential effects on cell death. (D) Advanced atherosclerosis is characterized by defective clearance of apoptotic cells (AC). Several compounds stimulate AC scavenging and may prevent secondary necrosis and necrotic core formation. LDL, low-density lipoprotein; oxLDL, oxidized low density lipoprotein; ROS, reactive oxygen species.