BubR1 Controls Heart Development by Promoting Expression of Cardiogenesis Regulators

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Congenital heart defects are structural anomalies present at birth that can affect the function of heart. Aneuploidy is a significant risk factor for congenital defects. Mosaic variegated aneuploidy syndrome, caused by mutations in Bub1b (encoding BubR1, mitotic checkpoint protein), leads to such as septal However, molecular rationale how promote associated with mosaic syndrome remains unresolved. To study morphological, structural, and cellular consequences BubR1 deletion heart, we crossed mice carrying conditional alleles Nkx2.5-cre mice. Single-cell RNA sequencing was carried out determine differentially expressed genes biological processes various cell types developing Trajectory analysis differentiation trajectory knockout embryonic hearts. Finally, CellChat provided details on major signaling interactions were either absent or hyperactive Here, show cardiac-specific causes lethality due developmental stalling after cardiac looping maturation including chamber wall thickness, septation, trabeculation. transcriptomic profiling further revealed cardiomyocytes severely impacted suppression critical cardiogenesis genes. Hyperactivation Wnt hearts indicated disturbed homeostasis pathways essential proper tissue morphogenesis Taken together, these findings reveal crucial regulator development vivo, which ensures timing morphogenesis.

Language: Английский

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Knockdown of TGFB2 Attenuates Ischemic Heart Failure by Inhibiting Apoptosis

Cardiovascular Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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STAT3 expression is reduced in cardiac pericytes in HFpEF and its loss reduces cellular adhesion and induces pericyte senescence

FEBS Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart cases and is characterised by reduced pericyte coverage. While the contributions other cardiac cell types to HFpEF are well-studied, role pericytes remains less understood. Using murine single-nucleus RNA-sequencing study in HFpEF, we identified STAT3 expression as a hallmark pericytes. Mechanistic studies vitro revealed that deletion induces cellular senescence impairs adhesion, recapitulating HFpEF-like characteristics. These findings suggest crucial maintaining homeostasis highlight its reduction potential driver loss, defining feature HFpEF.

Language: Английский

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Keeps Cardiac Pericytes in Good Shape: Regulator of G-Protein Signaling-5

Circulation Research, Journal Year: 2024, Volume and Issue: 134(10), P. 1256 - 1258

Published: May 9, 2024

Language: Английский

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Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 5, 2024

Abstract Aims Aging is influenced by genetic determinants and comorbidities, among which diabetes increases the risk for heart failure with preserved ejection fraction. There no therapy to prevent dysfunction in aging diabetic individuals. In previous studies, a single administration of longevity-associated variant (LAV) human BPIFB4 gene halted decline older type 2 mice. Here, we asked whether orally administered LAV-BPIFB4 protein replicates these benefits. Materials Methods two controlled, randomized 18-month-old male C57BL/6 J mice 9-week-old C57BLKS/J-Leprdb/Leprdb/Dock7 + [db/db] both sexes underwent baseline echocardiography. They then received recombinant purified (3 µg/animal, every three days) or vehicle gavage. After 30 days, animals echocardiography, hearts were collected post-termination histology. Results All completed study except one female mouse, was culled prematurely because tooth malocclusion caused eating problems. effect on body weight studies glycosuria study. mice, increased myocardial Bpifb4 expression, improving contractility capillarity while reducing perivascular fibrosis senesce. improved systolic function, microvascular density, senescence, whereas benefit limited function females. Conclusions This shows feasibility efficacy associated longevity contrasting pivotal factors animal models. The revealed that sex influences treatment efficacy.

Language: Английский

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Ershen Zhenwu Decoction Suppresses Myocardial Fibrosis of Chronic Heart Failure with Heart–Kidney Yang Deficiency by Down-Regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases Signaling Pathway

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 340, P. 119146 - 119146

Published: Nov. 22, 2024

Language: Английский

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Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Aims: Aging is influenced by genetic determinants and comorbidities, among which diabetes increases the risk for heart failure with preserved ejection fraction. There no therapy to prevent dysfunction in ageing diabetic individuals. In previous studies, a single administration of longevity-associated variant (LAV) human BPIFB4 gene halted decline older type-2 mice. Here, we asked whether orally administered LAV-BPIFB4 protein replicates these benefits. Materials Methods.In two controlled, randomized 18-month-old male C57BL/6J mice 9-week-old C57BLKS/J-Leprdb/Leprdb/Dock7+ [db/db] both sexes underwent baseline echocardiography. They then received recombinant purified (3 µg/animal, every three days) or vehicle gavage. After 30-day, animals echocardiography hearts were collected post-termination histology. Results. All completed study except one female mouse, was culled prematurely because tooth malocclusion, caused eating problems. effect on body weight studies glycosuria study. aging mice, increased myocardial BPIFB4 expression, improving contractility capillarity while reducing perivascular fibrosis senesce. improved systolic function, microvascular density, senescence, whereas benefit limited function females. Conclusions. This shows feasibility efficacy associated longevity contrasting pivotal factors animal models. The revealed that sex influences treatment efficacy.

Language: Английский

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The aging heart: exploring the role of Klotho in cardiac health/function

The Journal of Cardiovascular Aging, Journal Year: 2024, Volume and Issue: 4(4)

Published: Dec. 20, 2024

This review discusses the pathophysiological changes associated with cardiac aging and potential therapeutic role of anti-aging protein Klotho. It highlights key contributors to heart failure, such as arterial stiffening, myocardial fibrosis, impaired relaxation, all which lead declining function heart. also explores regulation Klotho expression, its various forms, impact on health, emphasizing protective roles against oxidative stress, inflammation, remodeling. Klotho's a target for mitigating improving cardiovascular health in elderly is central theme, making it promising candidate future interventions aimed at enhancing longevity.

Language: Английский

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