Excessive training induces molecular signs of pathologic cardiac hypertrophy

2018 ◽  
Vol 233 (11) ◽  
pp. 8850-8861 ◽  
Author(s):  
Alisson L. da Rocha ◽  
Giovana R. Teixeira ◽  
Ana P. Pinto ◽  
Gustavo P. de Morais ◽  
Luciana da C. Oliveira ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Pathologic Cardiac Hypertrophy

Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice

2016 ◽  
Vol 421 (1-2) ◽  
pp. 55-65 ◽  
Author(s):  
Jung Woo Han ◽  
Young Ho Lee ◽  
Su-In Yoen ◽  
Joel Abramowitz ◽  
Lutz Birnbaumer ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Pathologic Cardiac Hypertrophy

scholarly journals TRPC channels are necessary mediators of pathologic cardiac hypertrophy

2010 ◽  
Vol 107 (15) ◽  
pp. 7000-7005 ◽  
Author(s):  
X. Wu ◽  
P. Eder ◽  
B. Chang ◽  
J. D. Molkentin
Keyword(s):  
Cardiac Hypertrophy ◽  
Trpc Channels ◽  
Pathologic Cardiac Hypertrophy

scholarly journals Cardiac Specific Overexpression of Transcription Factor EB (TFEB) in Normal Hearts Induces Pathologic Cardiac Hypertrophy and Lethal Cardiomyopathy

2021 ◽  
Author(s):  
Helena C. Kenny ◽  
Eric T. Weatherford ◽  
Greg V. Collins ◽  
Chantal Allamargot ◽  
Taha Gesalla ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Calcium Release ◽  
Left Ventricular ◽  
Heart Weight ◽  
Mitochondrial Morphology ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Regulatory Pathways ◽  
Pathologic Cardiac Hypertrophy

AbstractTFEB promotes lysosomal biogenesis, autophagy, and lysosomal exocytosis. The present study characterized the consequence of inducible TFEB overexpression in cardiomyocytes in vivo. We generated cardiomyocyte-specific doxycycline inducible (Tet off) mice to achieve spatial and temporal control of TFEB overexpression, by crossing TFEB transgenic mice with mice harboring the tTA transgene (TFEB/tTA). Two weeks after doxycycline removal, an 8-fold increase in TFEB protein expression was observed in transgenic hearts. Heart weight normalized to tibia length was increased by 2.5-fold following TFEB overexpression (TFEB/tTA), characterized by induction of markers of pathological hypertrophy, such as Nppa, Nppb and Acta1, progressive contractile dysfunction and cardiac dilatation. Overexpression of TFEB resulted in premature death, associated with high degree AV block. Reversal of TFEB overexpression normalized cardiac structure and function. Mitochondrial respiration and ATP levels were preserved after 2-weeks of TFEB induction, despite reduced mitochondrial (OXPHOS) protein expression, mtDNA content, and altered mitochondrial morphology. Signaling through mTOR was induced in TFEB/tTA mice, and when inhibited by rapamycin treatment for 4 weeks, partially offset left ventricular dysfunction. Transcriptome analysis revealed early suppression of mitochondrial metabolic pathways, induction of fibrosis and altered calcium signaling. MCOLN1, a lysosomal calcium release channel, the calcineurin target RCAN1.4, and the mitochondrial calcium uniporter (MCU) were strikingly induced in TFEB/tTA mice. In summary, persistent overexpression of TFEB at high levels (8-fold protein upregulation) in cardiomyocytes promotes pathologic cardiac hypertrophy via suppression of mitochondrial bioenergetic pathways and activation of pro-fibrotic and calcium regulatory pathways.

scholarly journals Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

2015 ◽  
Vol 462 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Brian L. Stauffer ◽  
Karen Dockstader ◽  
Gloria Russell ◽  
Jamie Hijmans ◽  
Lisa Walker ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Over Expression ◽  
Specific Manner ◽  
Pathologic Cardiac Hypertrophy

Abstract 104: Protein Kinase GIα Functions in the Cardiac Myocyte as a Tonic Inhibitor of Pathologic Cardiac Hypertrophy In Vivo

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Robert M Blanton ◽  
James P Mendoza ◽  
Mark Aronovitz ◽  
David A Kass ◽  
Michael E Mendelsohn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Cardiac Myocyte ◽  
Heart Weight ◽  
Cross Sectional ◽  
Lv Remodeling ◽  
Exon 1 ◽  
Tibia Length ◽  
Pathologic Cardiac Hypertrophy

Objectives: We and others previously demonstrated that activation of the NO-cGMP-Protein Kinase G (PKG) pathway inhibits cardiac hypertrophy and remodeling in vivo. However, it remains untested whether PKG specifically in the cardiac myocyte (CM) mediates these effects. We therefore tested the hypothesis that PKGIα inhibits pathologic cardiac hypertrophy through a specific role in the CM. Methods and Results: We created and characterized mice with CM-restricted excision of PKGIα. Mice were generated in which the PKGI exon 1 (specific for the Iα isoform) was flanked by loxP sites. We crossed these PKGIα fl/fl mice with αMHC-Cre mice which constitutively express Cre recombinase selectively in the CM. The resultant PKGIα fl/fl / αMHC-Cre+/- mice were compared with PKGIα fl/fl / αMHC-Cre-/- littermate controls (termed PKG CMKO and Ctrl, respectively). By age 3 months (n=5 per genotype), male PKG CMKO mice developed atrial and LV hypertrophy compared with Ctrl littermates PKG CMKO atrial weight/tibia length 0.33 ± 0.03 mg/mm vs 0.22 ± .01 in Ctrl, P <0.05; PKG CMKO LV/TL 5.0 ± 0.2 mg/mm vs 4.1 ± 0.4 in Ctrl, P <0.05). LV CM cross sectional area also increased in the 3 month old PKG CMKO mice (9445 ± 282 pixels PKG CMKO vs 8273 ± 213 in Ctrl, n>400 cells/genotype, 5 hearts per genotype; P <0.001). The systolic index end systolic elastance was decreased in 3 month old PKG CMKO mice (PKG CMKO 3.1 ± 0.4 mmHg/μ l vs 6.1 ± 1.0 in Ctrl-; P <0.05). Importantly, blood pressure did not differ between genotypes. By age 6 months, PKG CMKO mice developed early mortality (3 of 4 PKG CMKO males died at 6 months of age vs 0 of 4 Ctrl males). Total heart and atrial weights of male mice (n=3 PKG CMKO , 4 Ctrl) increased in PKG CMKO mice (heart weight/tibia length 10.8 ± 1.7 mg/mm in PKG CMKO vs 7.1 ± 0.6 in Ctrl; P <0.05; atrial weight/tibia length 2.3 ± 1.1 mg/mm in PKG CMKO vs 0.30 ± 0.1 Ctrl, P <0.05). LV fractional shortening percentage, recorded at 6 months age, trended lower in the PKG CMKO mice as well (35 ± 3% PKG CMKO vs 44 ± 4% Ctrl, P 0.09). Conclusions: These data provide the first evidence that PKGIα functions in the CM as a tonic inhibitor of age-dependent pathologic hypertrophy, supporting further study of PKGIα as a therapeutic target in the prevention and treatment of LV remodeling and congestive heart failure.

scholarly journals Caspase Cleavage of Gelsolin Is an Inductive Cue for Pathologic Cardiac Hypertrophy

2018 ◽  
Vol 7 (23) ◽  
Author(s):  
Charis Putinski ◽  
Mohammad Abdul‐Ghani ◽  
Steve Brunette ◽  
Patrick G. Burgon ◽  
Lynn A. Megeney
Keyword(s):  
Cardiac Hypertrophy ◽  
Caspase Cleavage ◽  
Pathologic Cardiac Hypertrophy

Abstract 15863: Macrophage Foxp1 is a Regulator of Pathologic Cardiac Hypertrophy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shuichi Yoneda ◽  
Saptarsi M Haldar ◽  
Jessica Jenkins ◽  
Yunmei Wang ◽  
Teruo Inoue ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Disease Process ◽  
Left Ventricular ◽  
Negative Regulator ◽  
Control Male ◽  
Pathologic Cardiac Hypertrophy

Introduction: Pathologic cardiac hypertrophy is a maladaptive response to neurohormonal and hemodynamic stress that is a hallmark of human heart failure. While inflammation has been implicated in pathologic hypertrophy, the molecular mechanisms underlying innate immune dysregulation in this disease process are incompletely defined. We have previously demonstrated that the forkhead transcription factor Foxp1 controls monocyte differentiation and suppresses inflammatory activation of macrophages. In this study, we hypothesized that monocyte/macrophage Foxp1 regulates pathologic cardiac hypertrophy. Methods: Macrophage-specific Foxp1 over-expressing (macFoxp1tg=anti-inflammatory) vs. non-tg controls, as well as macrophage-specific Foxp1 knockdown (macFoxp1ko=pro-inflammatory) vs. Cre-control male mice were subject to chronic angiotensin II (AII) infusion (1.8 mcg/kg/min via subcutaneous osmotic mini-pump) for 4 weeks. Results: AII-mediated cardiac hypertrophy (heart mass and cardiomyocyte cross-sectional area), left ventricular (LV) systolic dysfunction, LV dilation, interstitial fibrosis and macrophage (Mac-3+ cells) accumulation were significantly attenuated in macFoxp1tg mice compared to non-tg controls. In contrast, AII-mediated cardiac hypertrophy, LV systolic dysfunction and cavity dilation were significantly exacerbated in macFoxp1ko mice compared to Cre controls. There were no differences in systemic blood pressure between these groups, corroborating a load-independent role for macrophage Foxp1 in cardiac hypertrophy. Conclusion: These studies identify macrophage Foxp1 as a novel negative regulator of pathologic cardiac hypertrophy in vivo. Modulation of Foxp1 signaling may provide a novel strategy for prevention and treatment of heart failure.

scholarly journals Activation of a HIF1α-PPARγ Axis Underlies the Integration of Glycolytic and Lipid Anabolic Pathways in Pathologic Cardiac Hypertrophy

2009 ◽  
Vol 9 (6) ◽  
pp. 512-524 ◽  
Author(s):  
Jaya Krishnan ◽  
Marianne Suter ◽  
Renata Windak ◽  
Tatiana Krebs ◽  
Allison Felley ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Pathologic Cardiac Hypertrophy
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