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Cecilia M Giachelli - One of the best experts on this subject based on the ideXlab platform.
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elevated extraCellular calcium levels induce Smooth Muscle Cell matrix mineralization in vitro
Kidney International, 2004Co-Authors: Hsueh Yang, Gabrielle Curinga, Cecilia M GiachelliAbstract:Elevated extraCellular calcium levels induce Smooth Muscle Cell matrix mineralization in vitro. Background Hyperphosphatemia, elevated calcium × phosphorus product (Ca × P), and calcium burden, major causes of vascular calcification, are correlated with increased cardiovascular morbidity and mortality in dialysis patients. Methods To address the underlying mechanisms responsible for these findings, we have utilized an in vitro human Smooth Muscle Cell (HSMC) model of vascular calcification. Previous studies using this system demonstrated enhanced calcification of HSMC cultures treated with phosphorus levels in the hyperphosphatemic range, and implicated a sodium-dependent phosphate cotransport-dependent mechanism in this effect. In the present study, we examine the effect of increasing calcium concentrations on HSMC calcification in vitro. Results Increasing calcium to levels observed in hypercalcemic individuals increased mineralization of HSMC cultures under normal phosphorus conditions. Importantly, at these total calcium concentrations, ionized calcium levels increased from 1.2 mmol/L to 1.7 mmol/L, consistent with levels observed physiologically in normocalcemic and hypercalcemic individuals, respectively. Furthermore, increasing both calcium and phosphorus levels led to accelerated and increased mineralization in the cultures. Calcium-induced mineralization was dependent on the function of a sodium-dependent phosphate cotransporter, since it was inhibited by phosphonoformic acid (PFA). While elevated calcium did not affect short-term phosphorus transport kinetics, long-term elevated calcium treatment of HSMCs induced expression of the sodium-dependent phosphate cotransporter, Pit-1. Conclusion These studies suggest that elevated calcium may stimulate HSMC mineralization by elevating Ca x P product and enhancing the sodium-dependent phosphate cotransporter-dependent mineralization pathway previously observed in HSMCs.
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Smooth Muscle Cell phenotypic transition associated with calcification upregulation of cbfa1 and downregulation of Smooth Muscle lineage markers
Circulation Research, 2001Co-Authors: Susie Steitz, Gabrielle Curinga, Hsueh Ying Yang, Mei Y Speer, Thorsten Schinke, Ruedi Aebersold, Paul A Haynes, Gerard Karsenty, Cecilia M GiachelliAbstract:Bovine aortic Smooth Muscle Cell (BASMC) cultures undergo mineralization on addition of the organic phosphate donor, β-glycerophosphate (βGP). Mineralization is characterized by apatite deposition ...
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Smooth Muscle Cell phenotypic transition associated with calcification: Upregulation of Cbfa1 and downregulation of Smooth Muscle lineage markers
Circulation Research, 2001Co-Authors: Susie A. Steitz, Gilles Karsenty, Gabrielle Curinga, Hsueh Ying Yang, Paul Haynes, Mei Y Speer, Thorsten Schinke, Ruedi Aebersold, Cecilia M GiachelliAbstract:Bovine aortic Smooth Muscle Cell (BASMC) cultures undergo mineralization on addition of the organic phosphate donor, beta-glycerophosphate (betaGP). Mineralization is characterized by apatite deposition on collagen fibrils and the presence of matrix vesicles, as has been described in calcified vascular lesions in vivo as well as in bone and teeth. In the present study, we used this model to investigate the molecular mechanisms driving vascular calcification. We found that BASMCs lost their lineage markers, SM22alpha and Smooth Muscle alpha-actin, within 10 days of being placed under calcifying conditions. Conversely, the Cells gained an osteogenic phenotype as indicated by an increase in expression and DNA-binding activity of the transcription factor, core binding factor alpha1 (Cbfa1). Moreover, genes containing the Cbfa1 binding site, OSE2, including osteopontin, osteocalcin, and alkaline phosphatase were elevated. The relevance of these in vitro findings to vascular calcification in vivo was further studied in matrix GLA protein null (MGP(-/-)) mice whose arteries spontaneously calcify. We found that arterial calcification was associated with a similar loss in Smooth Muscle markers and a gain of osteopontin and Cbfa1 expression. These data demonstrate a novel association of vascular calcification with Smooth Muscle Cell phenotypic transition, in which several osteogenic proteins including osteopontin, osteocalcin, and the bone determining factor Cbfa1 are gained. The findings suggest a positive role for SMCs in promoting vascular calcification.
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phosphate regulation of vascular Smooth Muscle Cell calcification
Circulation Research, 2000Co-Authors: Shuichi Jono, Marc D Mckee, Charles E Murry, Atsushi Shioi, Yoshiki Nishizawa, Katsuhito Mori, Hirotoshi Morii, Cecilia M GiachelliAbstract:Abstract —Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extraCellular inorganic phosphate levels to regulate human aortic Smooth Muscle Cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org.
Jonathan H Jaggar - One of the best experts on this subject based on the ideXlab platform.
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Smooth Muscle Cell transient receptor potential polycystin 2 trpp2 channels contribute to the myogenic response in cerebral arteries
The Journal of Physiology, 2013Co-Authors: Damodaran Narayanan, Simon Bulley, Dennis M Leo, Sarah K Burris, Kyle S Gabrick, Frederick A Boop, Jonathan H JaggarAbstract:Key points • Intravascular pressure is reported to activate several mechanosensitive ion channels, leading to Smooth Muscle Cell (SMC) depolarization, voltage-dependent Ca2+ channel activation and vasoconstriction; a process known as the ‘myogenic response’. • Polycystin-1 and -2 (TRPP1 and -2) have been shown to differentially regulate the mesenteric artery myogenic response, with TRPP2 expression attenuating vasoconstriction. • We show that TRPP2 is the major TRPP isoform expressed and that TRPP2 is located primarily in the plasma membrane in cerebral artery SMCs. • Selective TRPP2 knockdown reduced swelling-induced non-selective cation currents (ICat) in SMCs and myogenic tone in cerebral arteries. • These data indicate that TRPP2 activation contributes to the cerebral artery myogenic response and suggest that TRPP2 performs differential functions in different vascular beds. Abstract Intravascular pressure-induced vasoconstriction is a Smooth Muscle Cell-specific mechanism that controls systemic blood pressure and organ regional blood flow. Smooth Muscle Cell polycystin-1 and -2 (TRPP1 and -2) proteins modulate the myogenic response in mesenteric arteries, but involvement in other vascular beds is unclear. Here, we examined TRPP2 expression, Cellular distribution, cation currents (ICat), and physiological functions in Smooth Muscle Cells of rat and human cerebral arteries. We demonstrate that TRPP2 is the major TRPP isoform expressed in cerebral artery Smooth Muscle Cells, with message levels higher than those of TRPP1. Arterial biotinylation and immunofluorescence indicated that TRPP2 is located primarily (∼88%) in the Smooth Muscle Cell plasma membrane. RNA interference reduced TRPP2 expression by ∼55% compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca2+ (CaV1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)−1) bath solution stimulated Gd3+-sensitive ICat in Smooth Muscle Cells that were reduced by selective TRPP2 knockdown. TRPP2 knockdown did not alter myogenic tone at 20 mmHg but reduced tone between ∼28 and 39% over an intravascular pressure range between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter depolarization-induced (60 mmol l K+) vasoconstriction. In summary, we show that TRPP2 is expressed in Smooth Muscle Cells of resistance-size cerebral arteries, resides primarily in the plasma membrane, and contributes to the myogenic response. Data also suggest that TRPP2 differentially regulates the myogenic response in cerebral and mesenteric arteries.
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Smooth Muscle Cell transient receptor potential polycystin 2 trpp2 channels contribute to the myogenic response in cerebral arteries
The Journal of Physiology, 2013Co-Authors: Damodaran Narayanan, Simon Bulley, Dennis M Leo, Sarah K Burris, Kyle S Gabrick, Frederick A Boop, Jonathan H JaggarAbstract:Intravascular pressure-induced vasoconstriction is a Smooth Muscle Cell-specific mechanism that controls systemic blood pressure and organ regional blood flow. Smooth Muscle Cell polycystin-1 and -2 (TRPP1 and -2) proteins modulate the myogenic response in mesenteric arteries, but involvement in other vascular beds is unclear. Here, we examined TRPP2 expression, Cellular distribution, cation currents (ICat), and physiological functions in Smooth Muscle Cells of rat and human cerebral arteries. We demonstrate that TRPP2 is the major TRPP isoform expressed in cerebral artery Smooth Muscle Cells, with message levels higher than those of TRPP1. Arterial biotinylation and immunofluorescence indicated that TRPP2 is located primarily (∼88%) in the Smooth Muscle Cell plasma membrane. RNA interference reduced TRPP2 expression by ∼55% compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca(2+) (CaV1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)(-1)) bath solution stimulated Gd(3+)-sensitive ICat in Smooth Muscle Cells that were reduced by selective TRPP2 knockdown. TRPP2 knockdown did not alter myogenic tone at 20 mmHg but reduced tone between ∼28 and 39% over an intravascular pressure range between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter depolarization-induced (60 mmol l K(+)) vasoconstriction. In summary, we show that TRPP2 is expressed in Smooth Muscle Cells of resistance-size cerebral arteries, resides primarily in the plasma membrane, and contributes to the myogenic response. Data also suggest that TRPP2 differentially regulates the myogenic response in cerebral and mesenteric arteries.
Michelle P Bendeck - One of the best experts on this subject based on the ideXlab platform.
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deletion of discoidin domain receptor 2 does not affect Smooth Muscle Cell adhesion migration or proliferation in response to type i collagen
Cardiovascular Pathology, 2012Co-Authors: Guangpei Hou, David Wang, Michelle P BendeckAbstract:Abstract Collagen receptors expressed on vascular Smooth Muscle Cells include the discoidin domain receptors (DDR1 and DDR2). DDR1 is known to play important roles in mediating Smooth Muscle Cell responses to vascular injury, including neointimal hyperplasia, but much less is known about the function of DDR2. In this study, we harvested Smooth Muscle Cells from DDR2 wild-type and knockout mice and studied the Cells using in vitro models of migration and growth. There were no significant differences in the ability of Ddr2+/+ or Ddr2−/− Smooth Muscle Cells to attach to, migrate, or proliferate on type I collagen. Furthermore, neither matrix metalloproteinase (MMP) 2 nor MMP-9 activity nor type I collagen expression was different between the Cell types. We conclude that in vitro, endogenous DDR2 is not required for Smooth Muscle Cell hyperplastic responses to collagen.
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doxycycline alters vascular Smooth Muscle Cell adhesion migration and reorganization of fibrillar collagen matrices
American Journal of Pathology, 2006Co-Authors: Christopher Franco, Diane Mulholland, Guangpei Hou, Muzharul M Islam, Katey Donaldson, Michelle P BendeckAbstract:Remodeling of injured blood vessels is dependent on Smooth Muscle Cells and matrix metalloproteinase activity. Doxycycline is a broad spectrum matrix metalloproteinase inhibitor that is under investigation for the treatment of acute coronary syndromes and aneurysms. In the present study, we examine the mechanisms by which doxycycline inhibits Smooth Muscle Cell responses using a series of in vitro assays that mimic critical steps in pathological vascular remodeling. Doxycycline treatment dramatically increased Smooth Muscle Cell adhesion to the substrate, as evidenced by interference reflection microscopy and immunostaining for paxillin and phosphotyrosine. Cell aggregation was also potentiated after treatment with doxycycline. Treatment with 104 μmol/L doxycycline reduced thymidine uptake by 58% compared with untreated Cells (P < 0.05) and inhibited closure of a scrape wound made in a Smooth Muscle Cell monolayer by 20% (P < 0.05). Contraction of a three-dimensional collagen gel was used as an in vitro model for constrictive vessel remodeling, demonstrating that treatment with 416 μmol/L doxycycline for 12 hours inhibited collagen gel remodeling by 37% relative to control (P < 0.05). In conclusion, we have shown that doxycycline treatment leads to dramatically increased Smooth Muscle Cell adhesion, which in turn might limit responses in pathological vascular remodeling.
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Smooth Muscle Cell migration and matrix metalloproteinase expression after arterial injury in the rat
Circulation Research, 1994Co-Authors: Michelle P Bendeck, Nobuya Zempo, Alexander W Clowes, R E Galardy, Michael A ReidyAbstract:We have characterized matrix metalloproteinase expression in the rat carotid artery after two forms of arterial injury, balloon catheter denudation and nylon filament denudation. Gelatinolytic enzymes with molecular masses of 70 and 62 kD were produced constitutively in the rat carotid. Production of an 88-kD gelatinase was induced after balloon catheter injury, and proteinase production continued during the period of migration of Smooth Muscle Cells from the media to the intima, from 6 hours to 6 days after balloon catheter injury. In addition, a marked increase in 62-kD gelatinolytic activity was observed between 4 and 14 days after arterial injury. Gelatinase activities (88 and 62 kD) were also increased after nylon filament denudation but were markedly less after this injury than after balloon catheter injury. These results suggested a correlation between gelatinase activity and Smooth Muscle Cell migration after arterial injury. Administration of a metalloproteinase inhibitor after balloon catheter injury resulted in a 97% reduction in the number of Smooth Muscle Cells migrating into the intima. Therefore, we hypothesize that gelatinase expression directly facilitates Smooth Muscle Cell migration within the media and into the intima. These results suggest that gelatinases are involved in the vascular Smooth Muscle Cell activation and neointimal formation that characterize arterial tissue remodeling after injury.
Damodaran Narayanan - One of the best experts on this subject based on the ideXlab platform.
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Smooth Muscle Cell transient receptor potential polycystin 2 trpp2 channels contribute to the myogenic response in cerebral arteries
The Journal of Physiology, 2013Co-Authors: Damodaran Narayanan, Simon Bulley, Dennis M Leo, Sarah K Burris, Kyle S Gabrick, Frederick A Boop, Jonathan H JaggarAbstract:Key points • Intravascular pressure is reported to activate several mechanosensitive ion channels, leading to Smooth Muscle Cell (SMC) depolarization, voltage-dependent Ca2+ channel activation and vasoconstriction; a process known as the ‘myogenic response’. • Polycystin-1 and -2 (TRPP1 and -2) have been shown to differentially regulate the mesenteric artery myogenic response, with TRPP2 expression attenuating vasoconstriction. • We show that TRPP2 is the major TRPP isoform expressed and that TRPP2 is located primarily in the plasma membrane in cerebral artery SMCs. • Selective TRPP2 knockdown reduced swelling-induced non-selective cation currents (ICat) in SMCs and myogenic tone in cerebral arteries. • These data indicate that TRPP2 activation contributes to the cerebral artery myogenic response and suggest that TRPP2 performs differential functions in different vascular beds. Abstract Intravascular pressure-induced vasoconstriction is a Smooth Muscle Cell-specific mechanism that controls systemic blood pressure and organ regional blood flow. Smooth Muscle Cell polycystin-1 and -2 (TRPP1 and -2) proteins modulate the myogenic response in mesenteric arteries, but involvement in other vascular beds is unclear. Here, we examined TRPP2 expression, Cellular distribution, cation currents (ICat), and physiological functions in Smooth Muscle Cells of rat and human cerebral arteries. We demonstrate that TRPP2 is the major TRPP isoform expressed in cerebral artery Smooth Muscle Cells, with message levels higher than those of TRPP1. Arterial biotinylation and immunofluorescence indicated that TRPP2 is located primarily (∼88%) in the Smooth Muscle Cell plasma membrane. RNA interference reduced TRPP2 expression by ∼55% compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca2+ (CaV1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)−1) bath solution stimulated Gd3+-sensitive ICat in Smooth Muscle Cells that were reduced by selective TRPP2 knockdown. TRPP2 knockdown did not alter myogenic tone at 20 mmHg but reduced tone between ∼28 and 39% over an intravascular pressure range between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter depolarization-induced (60 mmol l K+) vasoconstriction. In summary, we show that TRPP2 is expressed in Smooth Muscle Cells of resistance-size cerebral arteries, resides primarily in the plasma membrane, and contributes to the myogenic response. Data also suggest that TRPP2 differentially regulates the myogenic response in cerebral and mesenteric arteries.
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Smooth Muscle Cell transient receptor potential polycystin 2 trpp2 channels contribute to the myogenic response in cerebral arteries
The Journal of Physiology, 2013Co-Authors: Damodaran Narayanan, Simon Bulley, Dennis M Leo, Sarah K Burris, Kyle S Gabrick, Frederick A Boop, Jonathan H JaggarAbstract:Intravascular pressure-induced vasoconstriction is a Smooth Muscle Cell-specific mechanism that controls systemic blood pressure and organ regional blood flow. Smooth Muscle Cell polycystin-1 and -2 (TRPP1 and -2) proteins modulate the myogenic response in mesenteric arteries, but involvement in other vascular beds is unclear. Here, we examined TRPP2 expression, Cellular distribution, cation currents (ICat), and physiological functions in Smooth Muscle Cells of rat and human cerebral arteries. We demonstrate that TRPP2 is the major TRPP isoform expressed in cerebral artery Smooth Muscle Cells, with message levels higher than those of TRPP1. Arterial biotinylation and immunofluorescence indicated that TRPP2 is located primarily (∼88%) in the Smooth Muscle Cell plasma membrane. RNA interference reduced TRPP2 expression by ∼55% compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca(2+) (CaV1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)(-1)) bath solution stimulated Gd(3+)-sensitive ICat in Smooth Muscle Cells that were reduced by selective TRPP2 knockdown. TRPP2 knockdown did not alter myogenic tone at 20 mmHg but reduced tone between ∼28 and 39% over an intravascular pressure range between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter depolarization-induced (60 mmol l K(+)) vasoconstriction. In summary, we show that TRPP2 is expressed in Smooth Muscle Cells of resistance-size cerebral arteries, resides primarily in the plasma membrane, and contributes to the myogenic response. Data also suggest that TRPP2 differentially regulates the myogenic response in cerebral and mesenteric arteries.
Gabrielle Curinga - One of the best experts on this subject based on the ideXlab platform.
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elevated extraCellular calcium levels induce Smooth Muscle Cell matrix mineralization in vitro
Kidney International, 2004Co-Authors: Hsueh Yang, Gabrielle Curinga, Cecilia M GiachelliAbstract:Elevated extraCellular calcium levels induce Smooth Muscle Cell matrix mineralization in vitro. Background Hyperphosphatemia, elevated calcium × phosphorus product (Ca × P), and calcium burden, major causes of vascular calcification, are correlated with increased cardiovascular morbidity and mortality in dialysis patients. Methods To address the underlying mechanisms responsible for these findings, we have utilized an in vitro human Smooth Muscle Cell (HSMC) model of vascular calcification. Previous studies using this system demonstrated enhanced calcification of HSMC cultures treated with phosphorus levels in the hyperphosphatemic range, and implicated a sodium-dependent phosphate cotransport-dependent mechanism in this effect. In the present study, we examine the effect of increasing calcium concentrations on HSMC calcification in vitro. Results Increasing calcium to levels observed in hypercalcemic individuals increased mineralization of HSMC cultures under normal phosphorus conditions. Importantly, at these total calcium concentrations, ionized calcium levels increased from 1.2 mmol/L to 1.7 mmol/L, consistent with levels observed physiologically in normocalcemic and hypercalcemic individuals, respectively. Furthermore, increasing both calcium and phosphorus levels led to accelerated and increased mineralization in the cultures. Calcium-induced mineralization was dependent on the function of a sodium-dependent phosphate cotransporter, since it was inhibited by phosphonoformic acid (PFA). While elevated calcium did not affect short-term phosphorus transport kinetics, long-term elevated calcium treatment of HSMCs induced expression of the sodium-dependent phosphate cotransporter, Pit-1. Conclusion These studies suggest that elevated calcium may stimulate HSMC mineralization by elevating Ca x P product and enhancing the sodium-dependent phosphate cotransporter-dependent mineralization pathway previously observed in HSMCs.
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Smooth Muscle Cell phenotypic transition associated with calcification upregulation of cbfa1 and downregulation of Smooth Muscle lineage markers
Circulation Research, 2001Co-Authors: Susie Steitz, Gabrielle Curinga, Hsueh Ying Yang, Mei Y Speer, Thorsten Schinke, Ruedi Aebersold, Paul A Haynes, Gerard Karsenty, Cecilia M GiachelliAbstract:Bovine aortic Smooth Muscle Cell (BASMC) cultures undergo mineralization on addition of the organic phosphate donor, β-glycerophosphate (βGP). Mineralization is characterized by apatite deposition ...
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Smooth Muscle Cell phenotypic transition associated with calcification: Upregulation of Cbfa1 and downregulation of Smooth Muscle lineage markers
Circulation Research, 2001Co-Authors: Susie A. Steitz, Gilles Karsenty, Gabrielle Curinga, Hsueh Ying Yang, Paul Haynes, Mei Y Speer, Thorsten Schinke, Ruedi Aebersold, Cecilia M GiachelliAbstract:Bovine aortic Smooth Muscle Cell (BASMC) cultures undergo mineralization on addition of the organic phosphate donor, beta-glycerophosphate (betaGP). Mineralization is characterized by apatite deposition on collagen fibrils and the presence of matrix vesicles, as has been described in calcified vascular lesions in vivo as well as in bone and teeth. In the present study, we used this model to investigate the molecular mechanisms driving vascular calcification. We found that BASMCs lost their lineage markers, SM22alpha and Smooth Muscle alpha-actin, within 10 days of being placed under calcifying conditions. Conversely, the Cells gained an osteogenic phenotype as indicated by an increase in expression and DNA-binding activity of the transcription factor, core binding factor alpha1 (Cbfa1). Moreover, genes containing the Cbfa1 binding site, OSE2, including osteopontin, osteocalcin, and alkaline phosphatase were elevated. The relevance of these in vitro findings to vascular calcification in vivo was further studied in matrix GLA protein null (MGP(-/-)) mice whose arteries spontaneously calcify. We found that arterial calcification was associated with a similar loss in Smooth Muscle markers and a gain of osteopontin and Cbfa1 expression. These data demonstrate a novel association of vascular calcification with Smooth Muscle Cell phenotypic transition, in which several osteogenic proteins including osteopontin, osteocalcin, and the bone determining factor Cbfa1 are gained. The findings suggest a positive role for SMCs in promoting vascular calcification.