Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice
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| Názov: | Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice |
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| Autori: | Han, Jung Woo, Lee, Young Ho, Yoen, Su-In, Abramowitz, Joel, Birnbaumer, Lutz, Lee, Min Goo, Kim, Joo Young |
| Prispievatelia: | College of Medicine, Dept. of Pharmacology, Jung Woo Han, Young Ho Lee, Su-In Yoen, Joel Abramowitz, Lutz Birnbaumer, Min Goo Lee, Joo Young Kim, Kim, Joo Young, Lee, Min Goo, Lee, Young Ho |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2016. |
| Rok vydania: | 2016 |
| Predmety: | Myocardium/pathology, 0301 basic medicine, Calcium Signaling, Calcium Channels, L-Type, Cardiomegaly/metabolism, Knockout, L-type Ca2+ channel, Cardiomegaly, Phenylephrine/metabolism, Transient Receptor Potential Canonical Channels 3, Pathologic Cardiac Hypertrophy, Mice, Phenylephrine, 03 medical and health sciences, Gene Expression Regulation, L-Type Ca2+ Channel, Animals, TRPC Cation Channels/deficiency, TRPC Cation Channels, L-Type/biosynthesis, Transient receptor potential canonical channels 3, Mice, Knockout, 0303 health sciences, Ca2+ Influx, L-Type/genetics, Myocardium, Ca2+ influx, Cardiomegaly/genetics, Mesenteric Arteries, 3. Good health, Mesenteric Arteries/pathology, Vasoconstriction, Mesenteric Arteries/metabolism, Myocardium/metabolism, Cardiomegaly/pathology, Calcium Channels, Vasoconstriction/genetics, Pathologic cardiac hypertrophy |
| Popis: | Sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) reprograms cardiovascular cell fate, leading to cellular hypertrophy via Ca(2+)-calmodulin/calcineurin (Cn)/NFAT activation. Accumulating evidence suggests that transient receptor potential canonical (Trpc) channels play important roles in the development of pathologic cardiac hypertrophy. Here, we demonstrated that Trpc3 mediates pathologic cardiac hypertrophy in neurohumoral elevation via direct regulation of CaV1.2 expressions. Elevated PE (phenylephrine) was maintained in mice by continuous infusion using an osmotic pump. Wild-type (WT) mice, but not Trpc3 (-/-) showed a sudden decrease in blood pressure (BP) or death following elevation of BP under conditions of elevated PE. Trpc3 (-/-) mesenteric artery showed decreased PE-stimulated vasoconstriction. Analysis of morphology, function, and pathologic marker expression revealed that PE elevation caused pathologic cardiac hypertrophy in WT mice, which was prevented by deletion of Trpc3. Interestingly, protection by Trpc3 deletion seemed to be a result of reduced cardiac CaV1.2 expressions. Basal and PE induced increased expression of protein and mRNA of CaV1.2 was decreased in Trpc3 (-/-) heart. Accordingly, altered expression of CaV1.2 was observed by knockdown or stimulation of Trpc3 in cardiomyocytes. These findings suggest that Trpc3 is a mediator of pathologic cardiac hypertrophy not only through mediating part of the Ca(2+) influx, but also through control of CaV1.2 expressions. |
| Druh dokumentu: | Article |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1573-4919 0300-8177 |
| DOI: | 10.1007/s11010-016-2784-0 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/27522668 https://europepmc.org/article/MED/27522668 https://link.springer.com/article/10.1007/s11010-016-2784-0/fulltext.html https://www.ncbi.nlm.nih.gov/pubmed/27522668 https://ri.conicet.gov.ar/handle/11336/39653 https://link.springer.com/article/10.1007/s11010-016-2784-0 https://pubmed.ncbi.nlm.nih.gov/27522668/ http://hdl.handle.net/11336/39653 |
| Rights: | Springer TDM CC BY NC SA CC BY NC ND |
| Prístupové číslo: | edsair.doi.dedup.....695600b0a027d7b440213d067d49742c |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) reprograms cardiovascular cell fate, leading to cellular hypertrophy via Ca(2+)-calmodulin/calcineurin (Cn)/NFAT activation. Accumulating evidence suggests that transient receptor potential canonical (Trpc) channels play important roles in the development of pathologic cardiac hypertrophy. Here, we demonstrated that Trpc3 mediates pathologic cardiac hypertrophy in neurohumoral elevation via direct regulation of CaV1.2 expressions. Elevated PE (phenylephrine) was maintained in mice by continuous infusion using an osmotic pump. Wild-type (WT) mice, but not Trpc3 (-/-) showed a sudden decrease in blood pressure (BP) or death following elevation of BP under conditions of elevated PE. Trpc3 (-/-) mesenteric artery showed decreased PE-stimulated vasoconstriction. Analysis of morphology, function, and pathologic marker expression revealed that PE elevation caused pathologic cardiac hypertrophy in WT mice, which was prevented by deletion of Trpc3. Interestingly, protection by Trpc3 deletion seemed to be a result of reduced cardiac CaV1.2 expressions. Basal and PE induced increased expression of protein and mRNA of CaV1.2 was decreased in Trpc3 (-/-) heart. Accordingly, altered expression of CaV1.2 was observed by knockdown or stimulation of Trpc3 in cardiomyocytes. These findings suggest that Trpc3 is a mediator of pathologic cardiac hypertrophy not only through mediating part of the Ca(2+) influx, but also through control of CaV1.2 expressions. |
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| ISSN: | 15734919 03008177 |
| DOI: | 10.1007/s11010-016-2784-0 |