A role for muscle LIM protein (MLP) in vascular remodeling.
Given the well-defined role of LIM-motif containing proteins in cytoskeletal organization, cell fate, and differentiation, we hypothesized that the regulation of LIM proteins played an integral role in vascular remodeling. We screened a compendium of cDNA microarray data from rat vascular smooth muscle cells (VSMC) for novel LIM-containing targets and identified muscle LIM protein (MLP), a gene previously thought to be only in striated muscle. Sequence analysis, RTQPCR and Western blotting reconfirmed expression of MLP in VSMC. MLP was elevated>10-fold 7 days following balloon injury in the rat carotid artery. Wire injury led to a significantly increased intima/media ratio in MLP -/- mice compared to wild-type controls (P<0.007, N=5). Fas-ligand and ceramide-induced apoptosis were significantly decreased in MLP deficient VSMC (n=6, P<0.001). Adenoviral-induced restoration of MLP significantly restored apoptotic response (N=6, P<0.001). These findings are the first to identify MLP in vascular smooth muscle and demonstrate that it plays a critical role in vascular remodeling. This is consistent with earlier findings demonstrating a role for MLP in striated muscle remodeling in response to load and stretch.
Wang
Xiaohong
X
Lillehei Heart Institute, Division of Cardiology, Department of Medicine, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 508, Minneapolis, MN 55455, USA.
Li
Qinglu
Q
Adhikari
Neeta
N
Hall
Jennifer L
JL
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002148:Calmodulin-Binding Proteins; D020212:Carotid Artery Injuries / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D033921:Vesicular Transport Proteins
D002148:Calmodulin-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C512945:Marcksl1 protein, mouse; C512942:Marcksl1 protein, rat; D008565:Membrane Proteins; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins