Induction of apoptosis in vascular smooth muscle cells by mechanical stretch. 2002

Mohammad Sotoudeh, and Yi-Shuan Li, and Noriyuki Yajima, and Chih-Chieh Chang, and Tsui-Chun Tsou, and Yibin Wang, and Shunichi Usami, and Anthony Ratcliffe, and Shu Chien, and John Y-J Shyy
Department of Bioengineering and Whitaker Institute of Biomedical Engineering, Advanced Tissue Sciences, La Jolla, California 92093, USA.

We studied the response of porcine vascular smooth muscle cells (PVSMCs) to cyclic sinusoidal stretch at a frequency of 1 Hz. Cyclic stretch with an area change of 25% caused an increase in PVSMC apoptosis, which was accompanied by sustained activation of c-Jun NH(2)-terminal kinases (JNK) and the mitogen-activated protein kinase p38. Cyclic stretch with an area change of 7% had no such effect. Infection of PVSMCs with recombinant adenoviruses expressing constitutively active forms of upstream molecules that activate JNK and p38 also led to apoptosis. The simultaneous blockade of both JNK and p38 pathways with adenovirus-mediated expression of dominant-negative mutants of c-Jun and p38 caused a significant decrease (to 1/2) of the apoptosis induced by 25% cyclic stretch. The 25% stretch also caused sustained clustering of tumor necrosis factor-alpha (TNF-alpha) receptor-1 and its association with TNF-alpha receptor-associated factor-2 (TRAF-2). Overexpressing the wild-type TRAF-2 in PVSMCs caused an increase in apoptosis. In contrast, the expression of a dominant-negative mutant of TRAF-2 attenuated stretch-induced apoptois. These results support the hypothesis that circumferential overload under hypertensive conditions induces a clustering of death receptors that cause vascular smooth muscle cell apoptosis.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008465 Mechanoreceptors Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptor cells include the INNER EAR hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with non-neural accessory structures. Golgi Tendon Organ,Golgi Tendon Organs,Krause's End Bulb,Krause's End Bulbs,Mechanoreceptor,Mechanoreceptor Cell,Meissner's Corpuscle,Neurotendinous Spindle,Neurotendinous Spindles,Receptors, Stretch,Ruffini's Corpuscle,Ruffini's Corpuscles,Stretch Receptor,Stretch Receptors,Mechanoreceptor Cells,Bulb, Krause's End,Bulbs, Krause's End,Cell, Mechanoreceptor,Cells, Mechanoreceptor,Corpuscle, Meissner's,Corpuscle, Ruffini's,Corpuscles, Ruffini's,End Bulb, Krause's,End Bulbs, Krause's,Krause End Bulb,Krause End Bulbs,Krauses End Bulb,Krauses End Bulbs,Meissner Corpuscle,Meissners Corpuscle,Organ, Golgi Tendon,Organs, Golgi Tendon,Receptor, Stretch,Ruffini Corpuscle,Ruffini Corpuscles,Ruffinis Corpuscle,Ruffinis Corpuscles,Spindle, Neurotendinous,Spindles, Neurotendinous,Tendon Organ, Golgi,Tendon Organs, Golgi
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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