Chronic Hypoxia Increases TRPC6 Expression and Basal Intracellular Ca2+ Concentration in Rat Distal Pulmonary Venous Smooth Muscle

Xu, Lei; Chen, Yuqin; Yang, Kai; Wang, Yingfeng; Tian, Lichun; Zhang, Jie; Wang, Elizabeth Wenqian; Sun, Dejun; Lu, Wenju; Wang, Jian

doi:10.1371/journal.pone.0112007

Cited by 16 publications

(23 citation statements)

References 35 publications

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“…VDCC blockers cannot decrease [Ca 2+ ] during CH, indicating that Ca 2+ influx occurs via signaling pathways other than VDCCs ( 8 – 10 ). In addition to VDCCs, HPV requires an influx of Ca 2+ via voltage-independent nonselective cation channels ( 6 , 11 – 15 ). These channels contribute to membrane depolarization during hypoxia.…”

Section: Introductionmentioning

confidence: 99%

TRPC6 is required for hypoxia-induced basal intracellular calcium concentration elevation, and for the proliferation and migration of rat distal pulmonary venous smooth muscle cells

Wang

Yan

et al. 2015

Molecular Medicine Reports

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Hypoxia induces pulmonary vasoconstriction and reconstruction in the pulmonary arteries and pulmonary veins (PVs), and elevation of intracellular calcium concentration ([Ca2+]i) is a primary factor of these processes. In the present study, the role of transient receptor potential cation channels (TRPCs) in mediating the hypoxia-induced elevation of [Ca2+]i in rat distal pulmonary venous smooth muscle cells (PVSMCs) was investigated. Rats with chronic hypoxic pulmonary hypertension (CHPH) were used for in vivo experiments, and PVSMCs were isolated for in vitro experiments. [Ca2+]i was measured using fura-2-based fluorescence calcium imaging. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels of TRPCs. Methyl thiazolyl tetrazolium and Transwell assays were used to investigate the proliferation and migration of PVSMCs, respectively. The results of the present study demonstrated that TRPC6 was increased in the distal PVs of CHPH rats, and in PVSMCs exposed to hypoxic conditions (4% O2, 72 h); however, TRPC1 was not. The 1-oleoyl-2-acetyl-sn-glycerol-induced [Ca2+]i elevation was increased in PVSMCs isolated from CHPH rats and in PVSMCs cultured under hypoxic conditions (4% O2, 72 h). Hypoxia induced PVSMC [Ca2+]i elevation, proliferation and migration. These alterations were inhibited following TRPC6 knockdown. Results from the present study suggest that TRPC6 expression is increased during chronic hypoxia, which contributes to Ca2+ entry into the cell, thus promoting proliferation and migration of PVSMCs.

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Section: Introductionmentioning

confidence: 99%

TRPC6 is required for hypoxia-induced basal intracellular calcium concentration elevation, and for the proliferation and migration of rat distal pulmonary venous smooth muscle cells

Wang

Yan

et al. 2015

Molecular Medicine Reports

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“…A recent study reports that TRPC6 upregulation was related to enhanced SOCE in rat hypoxic PVSMCs, which was not consistent with our observations. 24 However, the direct evidence confirming that TRPC6 mediates SOCE using siRNA to knockdown TRPC6, and the relationship between TRPC6 and ROCE in PVSMCs, were both absent. Moreover, it is unclear if TRPC6 displays a different phenotype in in vitro cultured PVSMCs; for example, by heteromerization with TRPC1 or TRPC4, which has been implicated in SOCE, 25 or if the enhanced SOCE in PVSMCs cultured in vitro for 60 h under hypoxic conditions results from altered expression of other TRP proteins including melastatinand vanilloid-TRP under in vitro conditions, which have also been implicated in SOCE.…”

Section: Ch Increases [Ca 2+ ]I and Roce In Pvsmcsmentioning

confidence: 99%

Chronic Hypoxia Increases Intracellular Ca2+ Concentration via Enhanced Ca2+ Entry Through Receptor-Operated Ca2+ Channels in Pulmonary Venous Smooth Muscle Cells

Peng

Wang

et al. 2015

Circ J

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2058PENG G et al. Circulation JournalOfficial Journal of the Japanese Circulation Society http://www. j-circ.or.jp arterial remodeling, less attention has been paid to the PV side in searching for the cellular and molecular mechanism of chronically hypoxic pulmonary venous remodeling. Editorial p 1910In pulmonary vascular smooth muscle cells, the increase in intracellular Ca 2+ concentration ([Ca 2+ ]i) is an essential signal for vasoconstriction and myocyte proliferation. The elevation of [Ca 2+ ]i could result from Ca 2+ influx from an extracellular source through Ca 2+ channels, such as L-type voltage-dependent Ca 2+ channels (VDCC), store-operated Ca 2+ channels (SOCC) and receptor-operated Ca 2+ channels (ROCC), or Ca 2+ release from internal storage sites, such as the sarcoplasmic ulmonary veins (PV) not only serve as conduits through which oxygenated capillary blood drains into the left atrium of the heart in pulmonary circulation, but they also play important roles in regulating both distention and recruitment of blood flow from alveolar wall capillaries and thus ventilation-perfusion matching in the lung. Studies reveal that PV exhibit vasoconstriction in response to various vasoconstrictor stimuli, such as endothelin, thromboxane, plateletactivating factor, leukotrienes and hypoxia. Exposure to chronic hypoxia (CH) causes vascular remodeling not only in pulmonary arteries (PA) but also in PV in a number of species including rat, sheep and humans, 1-4 and leads to hypoxic pulmonary hypertension (HPH). Despite the numerous progresses in elucidating the underlying mechanisms of CH-induced pulmonary

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“…In mild hypoxia-induced cardiomyocytes hypertrophy, TRPC3 and -6 up-regulations and enhanced calcium-calcineurin signals were inhibited by a hypoxia-inducible factor 1(HIF-1) specific blocker, whereas promoted by HIF-1α overexpression. Hypoxia triggered intracellular calcium contributes to promoted proliferation and migration of SMCs then make the vasoconstriction to increase blood pressure [32].…”

Section: Effects Of Trpc3 6 On Smcmentioning

confidence: 99%

TRPC3 and TRPC6 Contribute to the Pathogenesis of Hypertension

Zou¹,

Zhang²,

Guo³

2015

AJMB

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Recently studies found that TRPC3 and TRPC6 played an important role in cardiovascular disease. Hypertension, as a cardiovascular disease causing the highest morbidity and mortality, has close relationship with the expressions of TRPC3 and TRPC6. Unbalanced calcium homeostasis is the major factor of pathogenesis of hypertension. Changes of intracellular calcium concentration depend on calcium transmembrane transportation, intracellular calcium store releasing and other processes. TRPC3, TRPC6 molecules, as non-selective cation channels on the cell membranes, are involved in the processes. This review illustrated the functions of TRPC3 and TRPC6 on myocardial cells, smooth muscle cells and inflammatory cells in the development of hypertension, and the effects of drugs like sildenafil to provide a new way for the prevention and treatment of hypertension.

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Chronic Hypoxia Increases TRPC6 Expression and Basal Intracellular Ca2+ Concentration in Rat Distal Pulmonary Venous Smooth Muscle

Cited by 16 publications

References 35 publications

TRPC6 is required for hypoxia-induced basal intracellular calcium concentration elevation, and for the proliferation and migration of rat distal pulmonary venous smooth muscle cells

TRPC6 is required for hypoxia-induced basal intracellular calcium concentration elevation, and for the proliferation and migration of rat distal pulmonary venous smooth muscle cells

Chronic Hypoxia Increases Intracellular Ca<sup>2+</sup> Concentration via Enhanced Ca<sup>2+</sup> Entry Through Receptor-Operated Ca<sup>2+</sup> Channels in Pulmonary Venous Smooth Muscle Cells

TRPC3 and TRPC6 Contribute to the Pathogenesis of Hypertension

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