title: Mechanotransduction via the elastin-laminin receptor (ELR) in resistance arteries.
abstract: The arterial wall is composed of dynamically interacting cellular and acellular components that are necessary for the maintenance of vessel homeostasis. Two extracellular proteins in the vessel wall, elastin and laminin, play important structural roles. We recently established a role for the elastin-laminin receptor (ELR) in mechanotransduction of stretch in cultured vascular smooth muscle (VSM) (Am. J. Physiol.: Heart Circ. Physiol. 280(3) (2001) H1354). We found stretch-mediated signaling by the ELR decreased the expression of the proto-oncogene, c-fos, and subsequent cellular proliferation. However, the role for the ELR in mediating pressure-induced changes in gene expression in intact, isolated resistance vessels is unknown and the goal of this study was to ascertain this possibility. In this study, isolated rat cerebral (approximately 180 microm) and mesenteric (approximately 280 microm) arteries were pressurized to 65 mmHg (baseline) and this pressure was held for 2 h. After this equilibration, pressures were increased to either 80 mmHg (n=6) or 140 mmHg (n=6) for 30 min and transcript levels of c-fos and the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Elevation of pressure in the cerebral arteries decreased the c-fos/GAPDH ratio by 72% in the 140 mmHg group compared to the 80 mmHg control. Importantly, the decrease in c-fos expression was blocked by ELR peptide antagonists (VGVAPG or YIGSR, 10 microM, n=6). In contrast, the decrease in c-fos expression was not observed in the mesenteric resistance arteries. In these vessels, pressure (140 mmHg) increased the c-fos/GAPDH ratio (+68% compared to normotensive control, n=6). To account for the difference between the cerebral and mesenteric vessels, histological analysis of elastin fiber content was performed. Cerebral arteries have greater amounts of loose elastin fibers (fibers outside of the organized elastin laminae) in the tunica media compared to mesenteric arteries. This may explain the opposite stretch-induced responses of c-fos expression in these vessels. Stretch-induced ELR signaling may play a prominent role in vascular adaptations to hypertension in specific organ systems. Our data further suggest that ELR activation may represent a larger component of mechanosensitive signaling in the cerebral circulation than in the mesenteric circulation.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Spofford
authors.forename: William M
authors.initials: WM
authors.lastname: Chilian
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002536:Cerebral Arteries / Q000166:cytology / Q000502:physiology*; D046508:Culture Techniques; D004549:Elastin / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006487:Hemostasis / Q000502:physiology; D007797:Laminin / Q000502:physiology; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008638:Mesenteric Arteries / Q000166:cytology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000502:physiology*; D013314:Stress, Mechanical; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D007797:Laminin; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C477138:elastin-laminin receptor, rat; D004549:Elastin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases