The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

Bilirubin and Biliverdin Treatment of Atherosclerotic Diseases

“…1,2 Several authors suggest that abnormal proliferation of the VSMCs plays an important role in the very early stages of atherogenesis, leading to atherosclerosis which is the number one cause of morbidity and mortality in the western world. 3,4 A similar pathology appears to exist in restenosis after vessel manipulation as well as in chronic allograft vasculopathy, 1,5 where extensive proliferation of the VSMCs in the neointima causes narrowing of the vessels and leads to organ ischemia and subsequently to acute (e.g., stroke, myocardial infarction) or chronic (e.g., chronic allograft rejection) deterioration of organ function. 3 Reagents interrupting cell cycle progression in VSMCs have been successfully tested in various animal models and are currently being considered as approaches for the treatment of neointimal hyperplasia after coronary revascularization or dilatation/stenting of the carotid artery.…”

HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia

“…It is generally considered that cerebrovascular endothelial dysfunction in response to metabolic disturbances is a major pathological mechanism during the development and progression of diabetic stroke, which ultimately leads to the proliferation of vascular endothelial cells and the formation of atherosclerosis [8]. Meanwhile, the cell cycle is the final common entry into intimal hyperplasia, and plays a vital role in the formation of endothelial dysfunction and atherosclerosis [9]. Therefore, it is important to assess the precise role of the cell cycle in diabetic stroke, which might facilitate the development of an appropriate therapeutic strategy for diabetic stroke.…”

“…As such, an aberrant cell cycle leads to abundant apoptosis or tumorigenesis [10]. The cell cycle is a precisely programmed pathway that is regulated by multiple related signaling cascades [9]. Among these, the activation and regulation of cyclin/cyclin-dependent kinase (cyclin/Cdk) complexes are thought to be a central component of the cell cycle [11].…”

Arterial territory-specific phosphorylated retinoblastoma protein species and CDK2 promote differences in the vascular smooth muscle cell response to mitogens

“…Based on our data and previous observations that reduced expression of CDK2 in actively proliferating cells causes growth arrest, we hypothesized that CDK2 knockdown by siRNA in the SMCs of the coronary artery would cause these cells to behave more similarly to internal mammary SMCs, i.e., exhibiting lower Rb phosphorylation and reduced proliferative propensity. 22 We first tested for cytotoxicity in response to coronary artery SMC transfection with different amounts of CDK2 siRNAs and control siRNAs. A lactose dehydrogenase (LDH)-based cytotoxicity assay was performed on cells that were electroporated with 1, 2, 5, or 10 nM of siRNA.…”