CDKN2B Regulates TGFβ Signaling and Smooth Muscle Cell Investment of Hypoxic Neovessels.

Rationale: Genetic variation at the chromosome 9p21 cardiovascular risk locus has been associated with peripheral artery disease, but its mechanism remains unknown.

Objective: To determine whether this association is secondary to an increase in atherosclerosis, or it is the result of a separate angiogenesis-related mechanism.

Methods And Results: Quantitative evaluation of human vascular samples revealed that carriers of the 9p21 risk allele possess a significantly higher burden of immature intraplaque microvessels than carriers of the ancestral allele, irrespective of lesion size or patient comorbidity.

Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis.

Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. Here, we investigated the role of Cdnk2b in atherogenesis and found that in a mouse model of atherosclerosis, deletion of Cdnk2b promoted advanced development of atherosclerotic plaques composed of large necrotic cores.

The combination of 9p21.3 genotype and biomarker profile improves a peripheral artery disease risk prediction model.

Peripheral artery disease (PAD) is a highly morbid condition affecting more than 8 million Americans. Frequently, PAD patients are unrecognized and therefore do not receive appropriate therapies. Therefore, new methods to identify PAD have been pursued, but have thus far had only modest success.

Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation.

Objective: Genomewide association studies have implicated allelic variation at 9p21.3 in multiple forms of vascular disease, including atherosclerotic coronary heart disease and abdominal aortic aneurysm. As for other genes at 9p21.