C1q-TNF-Related Protein-9 Promotes Cardiac Hypertrophy and Failure.
BACKGROUND
Myocardial endothelial cells promote cardiomyocyte hypertrophy, possibly through the release of growth factors. The identity of these factors, however, remains largely unknown, and we hypothesized here that the secreted CTRP9 (C1q-tumor necrosis factor-related protein-9) might act as endothelial-derived protein to modulate heart remodeling in response to pressure overload.


OBJECTIVE
To examine the source of cardiac CTRP9 and its function during pressure overload.


RESULTS
CTRP9 was mainly derived from myocardial capillary endothelial cells. CTRP9 mRNA expression was enhanced in hypertrophic human hearts and in mouse hearts after transverse aortic constriction (TAC). CTRP9 protein was more abundant in the serum of patients with severe aortic stenosis and in murine hearts after TAC. Interestingly, heterozygous and especially homozygous knock-out C1qtnf9 (CTRP9) gene-deleted mice were protected from the development of cardiac hypertrophy, left ventricular dilatation, and dysfunction during TAC. CTRP9 overexpression, in turn, promoted hypertrophic cardiac remodeling and dysfunction after TAC in mice and induced hypertrophy in isolated adult cardiomyocytes. Mechanistically, CTRP9 knock-out mice showed strongly reduced levels of activated prohypertrophic ERK5 (extracellular signal-regulated kinase 5) during TAC compared with wild-type mice, while CTRP9 overexpression entailed increased ERK5 activation in response to pressure overload. Inhibition of ERK5 by a dominant negative MEK5 mutant or by the ERK5/MEK5 inhibitor BIX02189 blunted CTRP9 triggered hypertrophy in isolated adult cardiomyocytes in vitro and attenuated mouse cardiomyocyte hypertrophy and cardiac dysfunction in vivo, respectively. Downstream of ERK5, we identified the prohypertrophic transcription factor GATA4, which was directly activated through ERK5-dependent phosphorylation.


CONCLUSIONS
The upregulation of CTRP9 during hypertrophic heart disease facilitates maladaptive cardiac remodeling and left ventricular dysfunction and might constitute a therapeutic target in the future.
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Mahesh
M
Appari
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Astrid
A
Breitbart
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Florian
F
Brandes
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Malgorzata
M
Szaroszyk
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Natali
N
Froese
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Mortimer
M
Korf-Klingebiel
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Mona Malek
MM
Mohammadi
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Andrea
A
Grund
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Gesine M
GM
Scharf
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Honghui
H
Wang
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Carolin
C
Zwadlo
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Daniela
D
Fraccarollo
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Ulrike
U
Schrameck
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Mona
M
Nemer
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
G William
GW
Wong
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Hugo A
HA
Katus
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Kai C
KC
Wollert
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Oliver J
OJ
Müller
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.).
Johann
J
Bauersachs
From the Klinik für Kardiologie und Angiologie (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., D.F., U.S., K.C.W., J.B., J.H.) and Cluster of Excellence REBIRTH (M.A., A.B., F.B., M.S., N.F., M.K.-K., M.M.M., A.G., G.M.S., H.W., C.Z., U.S., K.C.W., J.B., J.H.), Medizinische Hochschule Hannover, Germany; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China (H.W.); Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada (M.N.); Department of Physiology and Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD (G.W.W.); Department of Cardiology, University Hospital Heidelberg, Germany (H.A.K., O.J.M.); and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (H.A.K., O.J.M.). Heineke.Joerg@Mh-Hannover.de.
Joerg
J
Heineke
D052242:Adiponectin / Q000096:biosynthesis*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006023:Glycoproteins / Q000096:biosynthesis*; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology
D052242:Adiponectin; C543615:C1QTNF9B protein, human; D006023:Glycoproteins; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
aortic valve stenosis; endothelial cells; hypertrophy; phosphorylation; signal transduction