Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA645891 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension [Affymetrix]
| PRJNA645893 | ENA
Project description:Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension [Illumina]
| PRJNA645894 | ENA
Project description:We assigned carboxypeptidase X 2 (Cpxm2) to a genetic locus for left ventricular mass. The functional role of Cpxm2 was investigated in Cpxm2-deficient (KO) and wild-type (WT) mice exposed to deoxycorticosterone acetate (DOCA)-salt hypertension and control conditions (SHAM). Both WT and KO animals developed severe and similar systolic hypertension in response to DOCA. WT mice developed severe LV damage. These changes were significantly ameliorated or even normalized (i.e. ejection fraction) in KO-DOCA animals. LV transcriptome analysis in WT, but not in KO mice, showed a molecular cardiac hypertrophy/remodeling signature with significant upregulation of 1234 transcripts including Cpxm2 in response to DOCA.
2023-07-10 | GSE154321 | GEO
Project description:Analysis of cardiac specific AT1 transgenic mice undergoing cardiac failure, cardiac hypertrophy and wild type aged matched controls. For detailed description of the AT1 Tg mice please refer to: Paradis P, Dali-Youcef N, Paradis FW, Thibault G, Nemer M. Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):931-6. PMID: 10639182 [PubMed - indexed for MEDLINE] Keywords: ordered
2005-06-15 | GSE2355 | GEO
Project description:Analysis of cardiac specific AT1 transgenic mice undergoing cardiac failure, cardiac hypertrophy and wild type aged matched controls. For detailed description of the AT1 Tg mice please refer to:; Paradis P, Dali-Youcef N, Paradis FW, Thibault G, Nemer M. Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):931-6. PMID: 10639182 [PubMed - indexed for MEDLINE]
2008-06-12 | E-GEOD-2355 | biostudies-arrayexpress
Project description:The tubulin code during cardiac hypertrophy and failure
| PRJNA800418 | ENA
Project description:Hypertrophic cardiomyopathy (HCM) is one of the most frequent inherited heart condition and a well-established risk factor for cardiovascular mortality worldwide. Although hypertrophy is traditionally regarded as an adaptive response to increased workload caused by physiological or pathological stress, prolonged hypertrophy can lead to heart failure characterized by impaired systolic function, increased apoptosis, fibrosis, ventricular dilation, and impaired metabolic substrate flexibility. While the key regulators for cardiac hypertrophy are well studied, the role of Prdm16 in this process remains poorly understood. In the present study, we demonstrate that Prdm16 is dispensable for cardiac development. However, it is required in the adult heart to preserve mitochondrial function and inhibit hypertrophy with advanced age. Cardiac-specific deletion of Prdm16 results in cardiac hypertrophy, excessive ventricular fibrosis, mitochondrial dysfunction, and impaired metabolic flexibility, leading to heart failure. We demonstrate that Prdm16 and euchromatic histone-lysine N- methyltransferase factors (Ehmts) act together to reduce the expression of fetal genes reactivated in pathological hypertrophy by inhibiting the functions of pro- hypertrophic transcription factor Myc. Although young Prdm16 knockout mice show normal cardiac function, they are predisposed to develop heart failure in response to metabolic stress. Collectively, our results demonstrate that Prdm16 protects the heart against age-dependent cardiac hypertrophy, fibrosis, mitochondrial dysfunction, adverse metabolic remodeling, and heart failure.
2020-09-21 | GSE153988 | GEO
Project description:Background: Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy regresses pre-existing cardiac hypertrophy, and prevents the progression to heart failure. Methods and Results: When male Dahl salt-sensitive (DSS) rats are fed a high salt (HS) diet, all rats develop cardiac hypertrophy after 5 weeks (H). Thereafter, rats were treated with vehicle (V), paricalcitol (PC, an active vitamin D analog at 200ng, IP 3x/wk), enalapril (EP, 90ug/day), and PC+EP. All groups were continued on the HS diet and evaluated after 4 weeks of therapy. The PC and PC+EP, but not the V and EP-only groups, showed significant regression of pre-existing cardiac hypertrophy. The signs of decompensated heart failure were evident in the vehicle-treated group; these heart failure parameters significantly improved with PC, EP or PC+EP therapy. The expression of PKCe, which is regulated by Ca2+ and known to stimulate cardiac hypertrophy, was significantly increased in the vehicle group, and PC, EP or PC+EP effectively decreased PKCe activation. We also observed normalization of genetic alterations during progression to heart failure with PC treatment. Conclusions: PC treatment resulted in both the regression of pre-existing cardiac hypertrophy, and the attenuation of the progression to heart failure, compared to improvement in progression to heart failure by EP alone. These beneficial findings in the heart were associated with inhibition of PKCe activation, and reversal of gene alterations. Male Dahl salt-sensitive rats (Harlan Sprague–Dawley, Somerville, NJ) were bred and fed a normal diet until 6 weeks of age. To generate pressure overload cardiac hypertrophy, they were then fed a high salt (6%NaCl) diet for the next 5 weeks. Data for baseline hypertrophic group (H) was obtained at the end of 11 weeks. Among H group animals, they were divided as follows and treated for an additional 4 weeks: 1) continuation of the HS diet with vehicle injection (H+V); 2) continuation of the HS diet with paricalcitol (19-nor-1,25-(OH)2 D2) (PC) (200ng IP 3x/wk) injection (H+PC); 3) continuation of the HS diet with low dose enalapril (EP), an angiotensin-converting enzyme inhibitor, infusion via osmotic pump and vehicle injection (H+EP+V); and 4) continuation of the HS diet with low dose EP infusion via osmotic pump and PC (200ng IP 3x/wk) injection (H+EP+PC). PC was prepared with 95% propylene glycol and 5% ethyl alcohol solution and administered three times a week on Monday, Wednesday, and Friday for 4 consecutive weeks. Vehicle groups received vehicle injections on the same schedule. Two groups of rats were implanted with pumps to deliver EP for 4 weeks. Since the reduction in blood pressure (BP) from high doses of EP would have effects on cardiac hypertrophy and progression to heart failure, we used low dose EP at 90ug/day, a maximum dose that did not significantly decrease BP in these rats, to study the effects of EP and PC that are independent of BP.
2010-09-14 | E-GEOD-24110 | biostudies-arrayexpress
Project description:Background: Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy regresses pre-existing cardiac hypertrophy, and prevents the progression to heart failure. Methods and Results: When male Dahl salt-sensitive (DSS) rats are fed a high salt (HS) diet, all rats develop cardiac hypertrophy after 5 weeks (H). Thereafter, rats were treated with vehicle (V), paricalcitol (PC, an active vitamin D analog at 200ng, IP 3x/wk), enalapril (EP, 90ug/day), and PC+EP. All groups were continued on the HS diet and evaluated after 4 weeks of therapy. The PC and PC+EP, but not the V and EP-only groups, showed significant regression of pre-existing cardiac hypertrophy. The signs of decompensated heart failure were evident in the vehicle-treated group; these heart failure parameters significantly improved with PC, EP or PC+EP therapy. The expression of PKCe, which is regulated by Ca2+ and known to stimulate cardiac hypertrophy, was significantly increased in the vehicle group, and PC, EP or PC+EP effectively decreased PKCe activation. We also observed normalization of genetic alterations during progression to heart failure with PC treatment. Conclusions: PC treatment resulted in both the regression of pre-existing cardiac hypertrophy, and the attenuation of the progression to heart failure, compared to improvement in progression to heart failure by EP alone. These beneficial findings in the heart were associated with inhibition of PKCe activation, and reversal of gene alterations.
2010-09-14 | GSE24110 | GEO
Project description:Heart failure is characterized by the inability of the heart to pump effectively and generate proper blood circulation to meet the body's needs; it is a devastating condition that affects more than 100 million people globally. In spite of this, little is known about the mechanisms regulating the transition from cardiac hypertrophy to heart failure. Previously, we identified a cardiomyocyte-enriched gene, CIP, which regulates cardiac homeostasis under pathological stimulation. Here, we show that the cardiac transcriptional factor GATA4 binds the promotor of CIP gene and regulates its expression. We further determined that both CIP mRNA and protein decrease in diseased human hearts. In a mouse model, induced cardiac-specific overexpression of CIP after the establishment of cardiac hypertrophy protects the heart by inhibiting disease progression toward heart failure. Transcriptome analyses revealed that the IGF, mTORC2 and TGFβ signaling pathways mediate the inhibitory function of CIP on pathologic cardiac remodeling. Our study demonstrates GATA4 as an upstream regulator of CIP gene expression in cardiomyocytes, as well as the clinical significance of CIP expression in human heart disease. More importantly, our investigation suggests CIP is a key regulator of the transition from cardiac hypertrophy to heart failure. The ability of CIP to intervene in the onset of heart failure suggests a novel therapeutic avenue of investigation forthe prevention of heart disease progression.
2022-03-05 | GSE194149 | GEO