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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Animals, Carotid Arteries, Carotid Artery Injuries, Cell Movement, Cell Proliferation, Cells, Cultured, Disease Models, Animal, Endothelial Cells, Enzyme Activation, Genotype, Guanine Nucleotide Exchange Factors, Hyperplasia, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Neointima, Neuropeptides, Phenotype, Phosphorylation, Protein Kinase Inhibitors, RNA Interference, Signal Transduction, Transfection, p21-Activated Kinases, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, rho GTP-Binding Proteins.
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Does kalirin promote neointimal hyperplasia by activating Rac in smooth muscle cells? Context: Kalirin is a multifunctional protein that contains 2 guanine nucleotide exchange factor domains for the GTPases Rac1 and RhoA. Variants of KALRN have been associated with atherosclerosis in humans, but Kalirin's activity has been characterized almost exclusively in the central nervous system. We therefore tested the hypothesis that Kalirin functions as a Rho-guanine nucleotide exchange factor in arterial smooth muscle cells (SMCs). Kalirin-9 protein is expressed abundantly in aorta and bone marrow, as well as in cultured SMCs, endothelial cells, and macrophages. Moreover, arterial Kalirin was upregulated during early atherogenesis in apolipoprotein E-deficient mice. In cultured SMCs, signaling was affected similarly in 3 models of Kalirin loss-of-function: heterozygous Kalrn deletion, Kalirin RNAi, and treatment with the Kalirin Rho-guanine nucleotide exchange factor -1 inhibitor 1-(3-nitrophenyl)-1H-pyrrole-2,5-dione. With reduced Kalirin function, SMCs showed normal RhoA activation but diminished Rac1 activation, assessed as reduced Rac-GTP levels, p21-activated kinase autophosphorylation, and SMC migration. Kalrn(-/+) SMCs proliferated 30% less rapidly than wild-type SMCs. Neointimal hyperplasia engendered by carotid endothelial denudation was ≈60% less in Kalrn(-/+) and SMC-specific Kalrn(-/+) mice than in control mice.
assistant
Kalirin functions as a guanine nucleotide exchange factor for Rac1 in SMCs, and promotes SMC migration and proliferation both in vitro and in vivo. Final Decision: yes