scholarly journals Chronic hypoxia and VEGF differentially modulate abundance and organization of myosin heavy chain isoforms in fetal and adult ovine arteries

2012 ◽  
Vol 303 (10) ◽  
pp. C1090-C1103 ◽  
Author(s):  
Margaret C. Hubbell ◽  
Andrew J. Semotiuk ◽  
Richard B. Thorpe ◽  
Olayemi O. Adeoye ◽  
Stacy M. Butler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Chronic Hypoxia ◽  
Myosin Heavy Chain Isoforms ◽  
Wall Structure ◽  
Vegf Receptor ◽  
Age Dependent ◽  
Endothelial Growth Factor

Chronic hypoxia increases vascular endothelial growth factor (VEGF) and thereby promotes angiogenesis. The present study explores the hypothesis that hypoxic increases in VEGF also remodel artery wall structure and contractility through phenotypic transformation of smooth muscle. Pregnant and nonpregnant ewes were maintained at sea level (normoxia) or 3,820 m (hypoxia) for the final 110 days of gestation. Common carotid arteries harvested from term fetal lambs and nonpregnant adults were denuded of endothelium and studied in vitro. Stretch-dependent contractile stresses were 32 and 77% of normoxic values in hypoxic fetal and adult arteries. Hypoxic hypocontractility was coupled with increased abundance of nonmuscle myosin heavy chain (NM-MHC) in fetal (+37%) and adult (+119%) arteries. Conversely, hypoxia decreased smooth muscle MHC (SM-MHC) abundance by 40% in fetal arteries but increased it 123% in adult arteries. Hypoxia decreased colocalization of NM-MHC with smooth muscle α-actin (SM-αA) in fetal arteries and decreased colocalization of SM-MHC with SM-αA in adult arteries. Organ culture with physiological concentrations (3 ng/ml) of VEGF-A165 similarly depressed stretch-dependent stresses to 37 and 49% of control fetal and adult values. The VEGF receptor antagonist vatalanib ablated VEGF's effects in adult but not fetal arteries, suggesting age-dependent VEGF receptor signaling. VEGF replicated hypoxic decreases in colocalization of NM-MHC with SM-αA in fetal arteries and decreases in colocalization of SM-MHC with SM-αA in adult arteries. These results suggest that hypoxic increases in VEGF not only promote angiogenesis but may also help mediate hypoxic arterial remodeling through age-dependent changes in smooth muscle phenotype and contractility.

Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia

2001 ◽  
Vol 90 (6) ◽  
pp. 2508-2513 ◽  
Author(s):  
Thomas L. Clanton ◽  
Valerie P. Wright ◽  
Peter J. Reiser ◽  
Paul F. Klawitter ◽  
Nanduri R. Prabhakar
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Intermittent Hypoxia ◽  
Contractile Function ◽  
Myosin Heavy Chain Isoforms ◽  
Adaptive Responses ◽  
Low Frequencies ◽  
Myosin Heavy Chain Isoform ◽  
Obstructive Sleep

Intermittent hypoxia (IH), associated with obstructive sleep apnea, initiates adaptive physiological responses in a variety of organs. Little is known about its influence on diaphragm. IH was simulated by exposing rats to alternating 15-s cycles of 5% O2 and 21% O2 for 5 min, 9 sets/h, 8 h/day, for 10 days. Controls did not experience IH. Diaphragms were excised 20–36 h after IH. Diaphragm bundles were studied in vitro or analyzed for myosin heavy chain isoform composition. No differences in maximum tetanic stress were observed between groups. However, peak twitch stress ( P < 0.005), twitch half-relaxation time ( P < 0.02), and tetanic stress at 20 or 30 Hz ( P < 0.05) were elevated in IH. No differences in expression of myosin heavy chain isoforms or susceptibility to fatigue were seen. Contractile function after 30 min of anoxia (95% N2-5% CO2) was markedly preserved at all stimulation frequencies during IH and at low frequencies after 15 min of reoxygenation. Anoxia-induced increases in passive muscle force were eliminated in the IH animals ( P < 0.01). These results demonstrate that IH induces adaptive responses in the diaphragm that preserve its function in anoxia.

scholarly journals Myosin heavy-chain isoforms in human smooth muscle

1989 ◽  
Vol 179 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Saverio SARTORE ◽  
Nicoletta DE MARZO ◽  
Anna Carmen BORRIONE ◽  
Anna Maria Cecilia ZANELLATO ◽  
Leopoldo SAGGIN ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Myosin Heavy Chain Isoforms

Hypertensive renal damage: Modulation expression of smooth muscle myosin heavy chain isoforms

Nephrology ◽  
1997 ◽  
Vol 3 (3) ◽  
pp. 251-259
Author(s):  
Naoe SUZUKI ◽  
Kenjiro KIMURA ◽  
Ryozo NAGAI ◽  
Shigeyoshi OHBA ◽  
Naobumi MISE ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Renal Damage ◽  
Myosin Heavy Chain Isoforms ◽  
Smooth Muscle Myosin ◽  
Muscle Myosin

Expression and function of COOH-terminal myosin heavy chain isoforms in mouse smooth muscle

2007 ◽  
Vol 293 (1) ◽  
pp. C238-C245 ◽  
Author(s):  
Anne F. Martin ◽  
Sunita Bhatti ◽  
Gail J. Pyne-Geithman ◽  
Mariam Farjah ◽  
Vlasios Manaves ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Immunoblot Analysis ◽  
Myosin Heavy Chain Isoforms ◽  
Smooth Muscle Myosin ◽  
Tail Region ◽  
Protein Ratio ◽  
Muscle Myosin

Isoforms of the smooth muscle myosin motor, SM1 and SM2, differ in length at the carboxy terminal tail region. Their proportion changes with development, hormonal status and disease, but their function is unknown. We developed mice carrying the myosin heavy chain (MyHC) transgenes SM1, cMyc-tagged SM1, SM2, and V5-tagged SM2, and all transgenes corresponded to the SMa NH2-terminal isoform. Transgene expression was targeted to smooth muscle by the smooth muscle α-actin promoter. Immunoblot analysis showed substantial expression of the cMyc-tagged SM1 and V5-tagged SM2 MyHC protein in aorta and bladder and transgene mRNA was expressed in mice carrying unlabeled SM1 or SM2 transgenes. Despite significant protein expression of tagged MyHCs we found only small changes in the SM1:SM2 protein ratio. Significant changes in functional phenotype were observed in mice carrying unlabeled SM1 or SM2 transgenes. Force in aorta and bladder was increased (72 ± 14%, 92 ± 11%) in SM1 and decreased to 57 ± 1% and 80 ± 3% in SM2 transgenic mice. SM1 transgenic bladders had faster (1.8 ± 0.3 s) and SM2 slower (7.1 ± 0.5 s) rates of force redevelopment following a rapid step shortening. We hypothesize that small changes in the SM1:SM2 ratio could be amplified if they are associated with changes in thick filament assembly and underlie the altered contractility. These data provide evidence indicating an in vivo function for the COOH-terminal isoforms of smooth muscle myosin and suggest that the SM1:SM2 ratio is tightly regulated in smooth muscle tissues.

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