Modulation of Abnormal Vasoconstriction Through 2‐Hydroxyisobutyrylation of Tropomyosin 3 Lys141: Targeting Histone Deacetylase 3 as a Key Approach DOI Creative Commons

Pan‐Pan Pang,

Jiangxin Liu, Wenbin Su

et al.

Journal of the American Heart Association, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 25, 2024

Background TPM3 (tropomyosin 3) is an actin‐binding protein in vascular smooth muscle cells, where posttranslational modifications critically regulate its actin affinity, influencing cardiovascular function. Emerging evidence suggests that Khib (2‐hydroxyisobutyrylation) plays a significant role the system. Histone deacetylase 3 (HDAC3) serves as “eraser” of marks. However, impact de‐2‐hydroxyisobutyrylation on contraction remains unclear. Methods and Results In this study, we employed mouse models vitro experiments to elucidate mechanism by which phenylephrine‐induced HDAC3 activation drives vasoconstriction via TPM3. Our findings demonstrate phenylephrine triggers nuclear export promotes interaction with TPM3, resulting decreased modification enhanced vasoconstriction. Coimmunoprecipitation confirmed reduces levels aorta. Additionally, ex vivo tension assays using aortic rings revealed treatment donor, ethyl 2‐hydroxyisobutyrate, induces endothelium‐independent vasodilation ameliorates hypertensive dysfunction. Molecular docking kinetic simulations identified Lys141 primary site targeted HDAC3‐mediated de‐2‐hydroxyisobutyrylation. This was further validated adenoviral transfection isolated blood vessels Lys141‐mutated construct, abolished effects contractility. Conclusions These underscore critical suggest modulating could provide novel therapeutic strategy for

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
Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases DOI Open Access
Zeyu Zhang, Zhihua Yang, Shuai Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116761 - 116761

Published: May 23, 2024

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form regulated by excessive lipid peroxidation, been shown to drive development multiple CVDs. This review provides insights into evolution concept similarities and differences with traditional modes programmed (e.g., apoptosis, autophagy, necrosis), as well core mechanisms ferroptosis (including cystine/glutamate transporter blockade, imbalance iron metabolism, peroxidation). In addition, it not only a detailed role its potential widely studied CVDs such coronary atherosclerotic heart disease, myocardial infarction, ischemia/reperfusion injury, failure, cardiomyopathy, aortic aneurysm but also overview phenomenon perspectives lesser-addressed cardiac valvulopathy, pulmonary hypertension, sickle disease. article aims integrate this knowledge provide comprehensive view wide range progress strategies field.

Language: Английский

Citations

4
Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy DOI

Jingjing Jiang,

Shengnan Hu, Kaibo Hu

et al.

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

Citations

0
Pulmonary Hypertension: Molecular Mechanisms and Clinical Studies DOI Creative Commons
Joseph Adu‐Amankwaah,

Qiang You,

Xinying Liu

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Pulmonary hypertension (PH) stands as a tumor paradigm cardiovascular disease marked by hyperproliferation of cells and vascular remodeling, culminating in heart failure. Complex genetic epigenetic mechanisms collectively contribute to the disruption pulmonary homeostasis. In recent years, advancements research technology have identified numerous gene deletions mutations, addition bone morphogenetic protein receptor type 2, that are closely associated with remodeling process PH. Additionally, modifications such RNA methylation, DNA histone modification, noncoding RNAs been shown precisely regulate PH molecular networks cell-type-specific manner, emerging potential biomarkers therapeutic targets. This review summarizes analyzes roles currently genes factors PH, emphasizing pivotal role long ncRNAs its regulation. it examines current clinical preclinical therapies for targeting these explores new treatment strategies.

Language: Английский

Citations

0
Mitochondrial medicine: “from bench to bedside” 3PM-guided concept DOI Creative Commons

Qianwen Shao,

Marie Louise Ndzie Noah, Olga Golubnitschaja

et al.

The EPMA Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

Citations

0
Natural products and ferroptosis: A novel approach for heart failure management DOI
Zeyu Zhang, Zhihua Yang, Shuai Wang

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156783 - 156783

Published: April 1, 2025

Language: Английский

Citations

0
TUFM in health and disease: exploring its multifaceted roles DOI Creative Commons
Ning Liu, Bo Pang,

Longfei Kang

et al.

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

Published: May 29, 2024

The nuclear-encoded mitochondrial protein Tu translation elongation factor, (TUFM) is well-known for its role in translation. Originally discovered yeast, TUFM demonstrates significant evolutionary conservation from prokaryotes to eukaryotes. Dysregulation of has been associated with disorders. Although early hypothesis suggests that localized within mitochondria, recent studies identify presence the cytoplasm, this subcellular distribution being linked distinct functions TUFM. Significantly, addition established function quality control, research indicates a broader involvement regulation programmed cell death processes (e.g., autophagy, apoptosis, necroptosis, and pyroptosis) diverse roles viral infection, cancer, other disease conditions. This review seeks offer current summary TUFM’s biological complex regulatory mechanisms human health disease. Insight into these intricate pathways controlled by may lead potential development targeted therapies range diseases.

Language: Английский

Citations

2
Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury DOI Creative Commons
Yan Huang, Guo Nan Yin, Fang‐Yuan Liu

et al.

Investigative and Clinical Urology, Journal Year: 2024, Volume and Issue: 65(4), P. 400 - 400

Published: Jan. 1, 2024

To determine whether the overexpression of Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI).

Language: Английский

Citations

2
The latest emerging drugs for the treatment of diabetic cardiomyopathy DOI
Minghao Li, Lin Liu, Chunyu Zhang

et al.

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(6), P. 641 - 654

Published: April 12, 2024

Introduction Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus involving multiple pathophysiologic mechanisms. In addition to hypoglycemic agents commonly used in diabetes, metabolism-related drugs, natural plant extracts, melatonin, exosomes, and rennin-angiotensin-aldosterone system are cardioprotective DCM. However, there lack systematic summarization drugs for

Language: Английский

Citations

1
Mitochondrial Sequencing Identifies Long Non-Coding RNA Features that Promote Binding to PNPase DOI
Andrew D. Taylor, Quincy A. Hathaway, Amina Kunovac

et al.

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 327(2), P. C221 - C236

Published: June 3, 2024

Long noncoding RNAs (lncRNAs) are relatively novel with increasingly prominent roles in regulating genetic expression, mainly the nucleus but more recently regions such as mitochondrion. This study explores how lncRNAs interact polynucleotide phosphorylase (PNPase), a protein that regulates RNA import into Machine learning identified several structural features improved lncRNA binding to PNPase, which may be useful targeting therapeutics

Language: Английский

Citations

1