Heparin Inhibits Lung Branching Morphogenesis: Potential Role of Smooth Muscle Cells in Cleft Formation

The mechanisms by which mitochondria regulate the sustained phase of agonist-induced responses in cytosolic Ca2+ concentration as an independent organelle in whole is not clear. By exposing to ethidium bromide and supplying pyruvate and uridine, we established mitochondrial DNA (mtDNA)-depleted rat airway smooth muscle cells (RASMCs) with maintained cellular energy. Upon an exposure to 2 μM histamine, [Ca2+]i in control RASMCs increased to a peak followed by a plateau above baseline, whereas [Ca2+]i in mtDNA-depleted RASMCs jumped to a peak and then declined to baseline without any plateau. mtDNA depletion apparently attenuated intracellular reactive oxygen species generation induced by histamine. By coexposure to 2 μM histamine and 0.1 μM exogenous H2O2, which did not affect [Ca2+]i by itself, the above difference in [Ca2+]i kinetics in mtDNA-depleted RASMCs was reversed. Intracellular H2O2 decomposition abolishes histamine-induced sustained elevation in [Ca2+]i in RASMCs. Thus, mitochondria regulate agonist-induced sustained [Ca2+]i elevation by a H2O2-dependent mechanism.

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Apolipoprotein E, Smooth Muscle Cells and the Pathogenesis of Cerebral Amyloid Angiopathy: the Potential Role of Impaired Cerebrovascular Abeta Clearance

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2000.tb06367.x ◽

2000 ◽

Vol 903 (1 VASCULAR FACT) ◽

pp. 180-186 ◽

Cited By ~ 25

Author(s):

REINHARD PRIOR ◽

GUNTHER WIHL ◽

BRITTA URMONEIT

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Apolipoprotein E ◽

Cerebral Amyloid Angiopathy ◽

Potential Role ◽

Muscle Cells ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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M270 DIFFERENTIAL EXPRESSION OF CAVEOLIN-1 IN UTERINE LEIOMYOMA AND MYOMETRIAL SMOOTH MUSCLE CELLS: THE POTENTIAL ROLE OF ESTROGEN

International Journal of Gynecology & Obstetrics ◽

10.1016/s0020-7292(12)61462-3 ◽

2012 ◽

Vol 119 ◽

pp. S619-S619

Author(s):

Y. Zhu

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Differential Expression ◽

Uterine Leiomyoma ◽

Potential Role ◽

Muscle Cells ◽

Caveolin 1

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Potential Role of PP2A in Regulating Ca 2+ ‐Activated Cl − Channels in Pulmonary Artery Smooth Muscle Cells

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.579.9 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Ramon Ayon ◽

William Sones ◽

Abigail Forrest ◽

Brian Perrino ◽

Maria Valencik ◽

...

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Potential Role ◽

Muscle Cells ◽

Cl Channels ◽

Pulmonary Artery Smooth Muscle

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Abstract 574: A Role for TWIST1 as GWAS Risk Gene for Coronary Artery Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.574 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Sylvia T Nurnberg ◽

Stephanie Testa ◽

Joebert Rosal ◽

Susannah Elwyn ◽

Wei Zhao ◽

...

Keyword(s):

Smooth Muscle ◽

Coronary Artery ◽

Smooth Muscle Cells ◽

Potential Role ◽

Muscle Cells ◽

Human Aorta ◽

Serum Starvation ◽

Genome Wide Association Studies ◽

Expression Levels

Genome-wide association studies (GWAS) have identified rs2107595 as association SNP for both stroke and cardiovascular disease. This polymorphism is located proximal to the HDAC9 gene, with TWIST1 106kb downstream as the next closest gene in the recombination interval. Whilst studies in hyperlipidemic Hdac9 knockout mice have demonstrated a pro-atherogenic effect of Hdac9, recent evidence suggests an additionally role of TWIST1 in atherosclerosis. For one, rs2107595 genotypes associate with differences in TWIST1 but not HDAC9 expression levels in human aorta (GTEx consortium, n=197, p=0.00016), proposing a role of TWIST1 downstream the association locus specifically in vascular smooth muscle cells. RNA-seq data from in vitro cultured human coronary artery smooth muscle (HCASMCs) and endothelial cells (HCAECs) shows differential expression of TWIST1 in smooth muscle cells (n=19/20, q=3E-60). Furthermore, TWIST1 expression is selectively upregulated in HCASMCs upon serum starvation, and TWIST1 protein is detected in human lesions both near the tunica media and at the fibrous cap where it co-localizes with smooth muscle actin (ACTA2). The GWAS association SNP is predicted to change transcription factor binding affinity from the more general E2F to RBPJ - a well-known modulator of Notch signaling in smooth muscle cells (Transfac professional, 2014.4 data release). The variant is located within an enhancer region in mesenchymal stem cells (Broad GSE17312), fibroblasts (UCSF-UBC-USD GSE16368) as well as in HCASMCs. Current studies explore the tissue-specific activity of this regulatory element through in vivo lacZ reporter assays to investigate a potential role in mouse coronary arteries. Genome editing studies in immortalized HCASMCs are being employed to investigate the effect of SNP genotype on expression levels of both TWIST1 and HDAC9. Future experiments using an inducible, smooth muscle specific knockout of Twist1 will interrogate the potential role of Twist1 in atherosclerosis.

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