ArticleCirculation2015
Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability.
Open access · greenAbstract read
In one paragraph
Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 81 citations in OpenAlex.
- Polycystin-1 and Cardiac Remodeling: From Mechanotransduction to Clinical Consequences.Circulation research · 2026Review
- Generation of Mice Harboring Bicc1 Conditional Null Alleles.Genesis (New York, N.Y. : 2000) · 2026Article
- Cardiac Localized Polycystin-2 in the Natriuretic Peptide Signaling Pathway and Hypertension.Journal of the American Society of Nephrology : JASN · 2025Article
- Progress on the mechanism of Polycystin-1 in bone remodeling.Frontiers in cell and developmental biology · 2025Review
- miR-338-5p regulated the NF-κB/MAPK pathway to alleviate inflammation and oxidative stress by targeting IL-6 in rats with atrial fibrillation.3 Biotech · 2024Article
- Cardiovascular perspectives of the TRP channel polycystin 2.The Journal of physiology · 2024Article
- Cardiovascular Manifestations and Management in ADPKD.Kidney international reports · 2023Review
- Calcium signaling in polycystic kidney disease- cell death and survival.Cell calcium · 2023Review
- Dynamic mechanobiology of cardiac cells and tissues: Current status and future perspective.Biophysics reviews · 2023Review
- Polycystin-1 Is a Crucial Regulator of BIN1 Expression and T-Tubule Remodeling Associated with the Development of Dilated Cardiomyopathy.International journal of molecular sciences · 2022Article
- Tracking N- and C-termini of C. elegans polycystin-1 reveals their distinct targeting requirements and functions in cilia and extracellular vesicles.PLoS genetics · 2022Article
- Mechanism of tethered agonist-mediated signaling by polycystin-1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Caveolin-3 prevents swelling-induced membrane damage via regulation of IBiophysical journal · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- Mechanoelectric coupling and arrhythmogenesis in cardiomyocytes contracting under mechanical afterload in a 3D viscoelastic hydrogel.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice.Scientific reports · 2021Article
- NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin.Cell death discovery · 2021Article
- Arrhythmogenic Hearts in PKD2 Mutant Mice Are Characterized by Cardiac Fibrosis, Systolic, and Diastolic Dysfunctions.Frontiers in cardiovascular medicine · 2021Article
- Polycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy.PloS one · 2021Article
- Deletion of cardiac polycystin 2/PC2 results in increased SR calcium release and blunted adrenergic reserve.American journal of physiology. Heart and circulatory physiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Zully PedrozoFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Alfredo CriolloFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Pavan K BattiproluFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Cyndi R MoralesFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Ariel Contreras-FerratFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Carolina FernándezFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Nan JiangFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Xiang LuoFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Michael J CaplanFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Stefan SomloFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Beverly A RothermelFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Thomas G GilletteFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT.
Sergio LavanderoFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT. joseph.hill@utsouthwestern.edu slavander@uchile.cl.
Joseph A HillFrom Division of Cardiology, Department of Internal Medicine (Z.P., A.C., P.K.B., C.R.M., N.J., X.L., B.A.R., T.G.G., S.L., J.A.H.) and Department of Molecular Biology (B.A.R., J.A.H.), UT Southwestern Medical Center, Dallas, TX; Advanced Center for Chronic Diseases and Centro de Estudios Moleculares de la Célula, Facultad de Medicina & Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile (Z.P., A.C.-F., C.F., S.L.); Instituto de Ciencias Biomédicas, Facultad de Medicina (Z.P., S.L.) and Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología (A.C.), Universidad de Chile, Santiago; and Departments of Cellular and Molecular Physiology (M.J.C.), Internal Medicine (S.S.), and Genetics (S.S.), Yale University School of Medicine, New Haven, CT. joseph.hill@utsouthwestern.edu slavander@uchile.cl.
Yale University · USAdvanced Center for Chronic Diseases · CL
Funding
Renal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI ARONSON, PETER S. · 2008 to 2022
$16.8MMicroenvironmental control of progenitors in organ dysfunction and repairU01HL100401 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI OLSON, ERIC N, SCHNEIDER, JAY W · 2009 to 2015
$8.3MModulating Calcineurin Signaling Pathways in MuscleR01HL072016 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI ROTHERMEL, BEVERLY A · 2003 to 2012
$3.7MMOUSE MODELS OF POLYCYSTIC KIDNEY DISEASE (PKD2)R01DK054053 · NIDDK · YESHIVA UNIVERSITY · PI SOMLO, STEFAN · 1998 to 2015
$3.2MHDAC Inhibition in Cardiac Hypertrophy and FailureR01HL080144 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2007 to 2011
$2.0MCalcineurin's role in circadian regulation of cardiac function and remodelingR01HL097768 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI ROTHERMEL, BEVERLY A · 2009 to 2012
$1.6MFoxo: Negative Regulator of Cardiac HypertrophyR01HL090842 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2009 to 2012
$1.6MSTIM1: Master Regulator of Calcium Homeostasis in CardiomyocytesR01HL120732 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2013 to 2016
$1.6MRodent Ultrasound Imaging SystemS10RR023729 · NCRR · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2009 to 2009
$290kNCRR NIH HHS S10 RR023729NHLBI NIH HHS HL-072016NHLBI NIH HHS HL-097768NHLBI NIH HHS HL-100401NHLBI NIH HHS HL-120732NHLBI NIH HHS R01 HL072016NHLBI NIH HHS R01 HL080144NHLBI NIH HHS R01 HL090842NHLBI NIH HHS R01 HL097768NHLBI NIH HHS R01 HL120732NHLBI NIH HHS U01 HL100401NIDDK NIH HHS DK-54053
Abstract
backgroundL-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress-induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes. METHODS AND
resultsWe subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and α1C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction-induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals
conclusionPC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein.
Indexed as
AnimalsAnimals, NewbornBiomarkersCalcium Channels, L-TypeCardiomegalyCells, CulturedFibrosisHypertrophyHypotonic SolutionsMaleMechanotransduction, CellularMiceMice, KnockoutMyocytes, CardiacProtein Interaction MappingProtein StabilityBiomarkersCalcium Channels, L-TypeHypotonic SolutionsL-type calcium channel alpha(1C)Recombinant Fusion ProteinsTRPP Cation Channelscardiomegalymechanotransduction, cellular
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.