Perivascular adipose tissue dysfunction contributes to thoracic aortic aneurysm development DOI Creative Commons
Zhenguo Wang,

Wenjuan Mu,

Ruiyan Xu

и другие.

Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)

Опубликована: Май 21, 2025

Abstract Background Thoracic aortic aneurysm (TAA) is a life-threatening disease with high morbidity and mortality rates due to fatal complications such as rupture. However, molecular mechanisms underlying TAA pathogenesis remain be fully elucidated. The aorta naturally surrounded by perivascular adipose tissue (PVAT), which produces releases adipokines other factors in paracrine manner that are pivotal for vascular physiology pathophysiology. Under healthy conditions, thoracic PVAT resembles brown (BAT) maintains homeostasis. In response pathogenic stimuli, can undergo whitening become dysfunctional, contributing the development of diseases. causal relationship between dysfunction pathogenesis, well mechanisms, unknown. This study investigated roles PPARg (a key determinant adipogenesis) PRDM16 adipocyte development) on development. Methods samples from patients were collected evaluated. Mice lacking those dysfunctional generated crossbreeding Ucp1 promoter-driven Cre mice Pparg floxed (brown adipocyte-specific knockout, BAKO ) Prdm16 ), respectively. formation was induced application porcine pancreatic elastase (PPE) evaluated through histological staining. Luciferase reporter assays chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) used determine target genes. Results We found near lesions exhibited reduced expression browning markers increased markers. showed impaired development, while displayed loss PVAT. Both aggravated formation. identified decorin, small proteoglycan extracellular matrix, transcriptional repressive gene PRDM16. decorin plasma patients. Conclusions maintenance brown-like characteristics necessary protect against contributes Our provides promising therapeutic strategy preventing progression inducing browning.

Язык: Английский

Blood pressure regulation through circadian variation: PRDM16 as a target in vascular smooth muscle cells DOI Creative Commons

M. Adriana Cuibus,

Omar Abdel‐Wahab

Journal of Clinical Investigation, Год журнала: 2025, Номер 135(3)

Опубликована: Фев. 2, 2025

The precise mechanisms of blood pressure (BP) regulation are not fully elucidated, and understanding BP is crucial for managing hypertension improving outcomes cardiovascular disease. In this issue the JCI, Wang et al. identified transcription factor PR domain-containing protein 16 (PRDM16) as a regulator both vascular smooth muscle cell contraction circadian response to control. PRDM16 directly transcriptionally controlled expression adrenergic receptor α 1d several clock genes regulation. These findings identify mechanism how molecular pathways govern variation, highlighting potential target hypertension.

Язык: Английский

Процитировано

0
Factors associated with blood pressure regulation in vascular smooth muscle cells DOI Creative Commons

Masaki Mogi,

Masayoshi Kukida

Hypertension Research, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Язык: Английский

Процитировано

0
Perivascular adipose tissue dysfunction contributes to thoracic aortic aneurysm development DOI Creative Commons
Zhenguo Wang,

Wenjuan Mu,

Ruiyan Xu

и другие.

Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)

Опубликована: Май 21, 2025

Abstract Background Thoracic aortic aneurysm (TAA) is a life-threatening disease with high morbidity and mortality rates due to fatal complications such as rupture. However, molecular mechanisms underlying TAA pathogenesis remain be fully elucidated. The aorta naturally surrounded by perivascular adipose tissue (PVAT), which produces releases adipokines other factors in paracrine manner that are pivotal for vascular physiology pathophysiology. Under healthy conditions, thoracic PVAT resembles brown (BAT) maintains homeostasis. In response pathogenic stimuli, can undergo whitening become dysfunctional, contributing the development of diseases. causal relationship between dysfunction pathogenesis, well mechanisms, unknown. This study investigated roles PPARg (a key determinant adipogenesis) PRDM16 adipocyte development) on development. Methods samples from patients were collected evaluated. Mice lacking those dysfunctional generated crossbreeding Ucp1 promoter-driven Cre mice Pparg floxed (brown adipocyte-specific knockout, BAKO ) Prdm16 ), respectively. formation was induced application porcine pancreatic elastase (PPE) evaluated through histological staining. Luciferase reporter assays chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) used determine target genes. Results We found near lesions exhibited reduced expression browning markers increased markers. showed impaired development, while displayed loss PVAT. Both aggravated formation. identified decorin, small proteoglycan extracellular matrix, transcriptional repressive gene PRDM16. decorin plasma patients. Conclusions maintenance brown-like characteristics necessary protect against contributes Our provides promising therapeutic strategy preventing progression inducing browning.

Язык: Английский

Процитировано

0