Mechanistic insights into the regression of atherosclerotic plaques DOI Creative Commons
Jianshu Song, Ce Cao, Ziyan Wang

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 19, 2024

Atherosclerosis is a major contributor to cardiovascular diseases and mortality globally. The progression of atherosclerotic disease results in the expansion plaques development necrotic cores. Subsequent plaque rupture can lead thrombosis, occluding blood vessels, end-organ ischemia with consequential ischemic injury. Atherosclerotic are formed by accumulation lipid particles overloaded subendothelial layer vessels. Abnormally elevated levels impaired endothelial function initial factors leading atherosclerosis. atherosclerosis research has never been interrupted, previous view was that pathogenesis an irreversible chronic process. However, recent studies have found be halted when patients' reversed normal or lower. A large number indicates it inhibit lesions promote regression cores lowering levels, improving repair ability vascular cells, promoting reverse cholesterol transport foam cells enhancing macrophages phagocytize clear core plaque. This article reviews progress on mechanism regression. Our goal provide guidance for developing better therapeutic approaches reviewing analyzing latest scientific findings.

Language: Английский

Roles of Sirtuins in Cardiovascular Diseases: Mechanisms and Therapeutics DOI

Yang-Nan Ding,

Hui-Yu Wang,

Xiaofeng Chen

et al.

Circulation Research, Journal Year: 2025, Volume and Issue: 136(5), P. 524 - 550

Published: Feb. 27, 2025

Cardiovascular diseases (CVDs) are experiencing a rapid surge and widely recognized as the leading cause of mortality in current aging society. Given multifactorial etiology CVDs, understanding intricate molecular cellular mechanisms is imperative. Over past 2 decades, many scientists have focused on Sirtuins, family nicotinamide adenine dinucleotide–dependent deacylases. Sirtuins highly conserved across species, from yeasts to primates, play crucial role linking diseases. participate nearly all key physiological pathological processes, ranging embryogenic development stress response aging. Abnormal expression activity exist aging-related diseases, while their activation has shown efficacy mitigating these (eg, CVDs). In terms research, this field maintained fast, sustained growth recent years, fundamental studies clinical trials. review, we present comprehensive, up-to-date discussion biological functions roles regulating cardiovascular biology CVDs. Furthermore, highlight latest advancements utilizing Sirtuin-activating compounds dinucleotide boosters potential pharmacological targets for preventing treating The unresolved issues field—from chemicobiological regulation Sirtuin-targeted CVD investigations—are also discussed. This timely review could be critical updated knowledge Sirtuin CVDs facilitating accessibility Sirtuin-targeting interventions.

Language: Английский

Citations

3
Targeting sirtuins for cancer therapy: epigenetics modifications and beyond DOI Creative Commons
Hui Shen,

Xinyi Qi,

Yue Hu

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(17), P. 6726 - 6767

Published: Jan. 1, 2024

Sirtuins (SIRTs) are well-known as nicotinic adenine dinucleotide

Language: Английский

Citations

9
Targeting mitochondrial ClpP: structural insights and therapeutic potential of ClpP agonists in cancer therapy DOI Creative Commons
Mo-Wei Kong, Yang Yu, Shuai Shao

et al.

Oncology Reviews, Journal Year: 2025, Volume and Issue: 19

Published: May 6, 2025

Mitochondrial "powerhouses" play a central function in cellular metabolism and energy generation. Their dysregulation is directly correlated with myriad of diseases, among them cancer. The serine protease ClpP, accompanied by its cochaperone ClpX, principal homeostatic regulator mitochondrial degrading aberrant proteins order to preserve integrity. Recently, evidence suggests ClpP overexpressed many cancer cells and, as such, an appealing target for drug therapy. In this review, current information about the structure, physiological function, therapeutic promise oncology summarized. We provide overview mechanistic rationale behind agonists novel anticancer drugs, their regulation cell signal transduction, major challenge creation small molecules that specifically activate human but not bacterial ClpP. review highlights approach therapy, presenting prospective potential treatment focusing on unexplored target.

Language: Английский

Citations

0
SM22α-Lineage Perivascular Stromal Cells Contribute to Abdominal Aortic Aneurysm DOI

Xiaoxi Pan,

Run Zhang,

Bingling Lu

et al.

Circulation Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

BACKGROUND: Perivascular adipose tissue (PVAT) is a key regulator of vascular dysfunction. Impairment PVAT phenotypic plasticity with aging may play role in pathology including abdominal aortic aneurysms (AAAs). Yet, the mechanisms underlying aneurysm pathogenesis remain elusive. METHODS: Single-cell RNA sequencing was performed on perivascular stromal cells from young (2- to 3-month-old) and aged (18- 20-month-old) mice. The expression PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) measured mice human samples. Loss- gain-of-function approaches were used investigate SM22α-lineage cell–derived development. Molecular explored through transcriptome functional studies mice, SM22α Cre ; Rosa26 RFP/+ PGC1α f/f Ang II (angiotensin II)–induced deoxycorticosterone acetate/salt-induced AAA models. RESULTS: + accumulated II–treated patients aneurysms. analysis revealed that disrupted differentiation potential led reduced levels. downregulation observed both mouse models lesions. In SM22α-driven deletion, II–induced formation accompanied by cell-to-myofibroblast differentiation. vitro knockdown suppressed nuclear YAP (Yes-associated protein) signaling, reducing adipocyte differentiation, while increasing MMP2 (matrix metalloproteinase 2)-secreting myofibroblasts. Furthermore, overexpression or administration signaling inhibitor verteporfin restored function conferred protection against formation. Last, we radiomics noninvasively evaluate context severity humans. CONCLUSIONS: deficiency disrupts balance between adipogenic myofibrogenic regulating ultimately promoting Radiomics assessment present promising noninvasive approach for evaluation aneurysms, offering valuable clinical research.

Language: Английский

Citations

0
Mechanistic insights into the regression of atherosclerotic plaques DOI Creative Commons
Jianshu Song, Ce Cao, Ziyan Wang

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 19, 2024

Atherosclerosis is a major contributor to cardiovascular diseases and mortality globally. The progression of atherosclerotic disease results in the expansion plaques development necrotic cores. Subsequent plaque rupture can lead thrombosis, occluding blood vessels, end-organ ischemia with consequential ischemic injury. Atherosclerotic are formed by accumulation lipid particles overloaded subendothelial layer vessels. Abnormally elevated levels impaired endothelial function initial factors leading atherosclerosis. atherosclerosis research has never been interrupted, previous view was that pathogenesis an irreversible chronic process. However, recent studies have found be halted when patients' reversed normal or lower. A large number indicates it inhibit lesions promote regression cores lowering levels, improving repair ability vascular cells, promoting reverse cholesterol transport foam cells enhancing macrophages phagocytize clear core plaque. This article reviews progress on mechanism regression. Our goal provide guidance for developing better therapeutic approaches reviewing analyzing latest scientific findings.

Language: Английский

Citations

3