Shared molecular, cellular, and environmental hallmarks in cardiovascular disease and cancer: any place for drug repurposing? DOI Creative Commons
Elisa Avolio, Barbara Bassani, Marzia Campanile

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 77(2), P. 100033 - 100033

Published: Dec. 24, 2024

Cancer and cardiovascular disease (CVD) are the 2 biggest killers worldwide. Specific treatments have been developed for diseases. However, mutual therapeutic targets should be considered because of overlap cellular molecular mechanisms. research has grown at a fast pace, leading to an increasing number new mechanistic treatments. Some these drugs could prove useful treating CVD, which realizes concept cancer drug repurposing. This review provides comprehensive outline shared hallmarks primarily ischemic heart failure. We focus on chronic inflammation, altered immune response, stromal vascular cell activation, underlying signaling pathways causing pathological tissue remodeling. There is obvious scope targeting those mechanisms, thereby achieving reciprocal preventive benefits. Major attention devoted illustrating logic, advantages, challenges, viable examples repurposing discussing potential influence sex, gender, age, ethnicity in realizing this approach. Artificial intelligence will help refine personalized application patients with CVD. SIGNIFICANCE STATEMENT: (CVD), worldwide, share several So far, specific therapies tackle development slow compared drugs. Understanding intersection between mechanisms diseases basis therapeutics CVD treatment. approach allow rapid CVDs.

Language: Английский

Role and Mechanism of Mitochondrial Ribosomal Proteins in Septic Myocardial Injury DOI Creative Commons
Longfei Wu, Junchao Huang,

Xiongfei Jia

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2677 - 2698

Published: Feb. 1, 2025

To investigate the role of mitochondrial ribosomal proteins (MRPs) in pathogenesis and progression septic myocardial injury. Additionally, we aim to propose new technical strategies experimental foundations for prevention treatment Animal cell models injury were established. Aberrantly expressed MRPs screened using transcriptome sequencing, their expression was verified by RT-qPCR Western blot. Subsequently, overexpressed knockdown constructed. The effects on CO I, PGC-1α, ATP content, ROS fluorescence intensity, membrane potential, GSDMD assessed, along with changes caspase-4 IL-1β levels. Transcriptome sequencing revealed a reduction mice Both blot analysis confirmed decreased animal Furthermore, overexpression both MRPS16 MRPL47 mitigated decrease I PGC-1α levels induced alleviated elevated IL-1β, caspase-4, caused findings suggest that can mitigate attenuating biosynthesis dysfunction, energy metabolism disorders, Ca2+ disturbances This ultimately reduces cellular damage alleviates

Language: Английский

Citations

0
Ca2+ Signaling in Cardiac Fibroblasts: An Emerging Signaling Pathway Driving Fibrotic Remodeling in Cardiac Disorders DOI Creative Commons
Francesco Moccia, Antonio Totaro, Germano Guerra

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 734 - 734

Published: March 17, 2025

Cardiac fibrosis is a scarring event that occurs in the myocardium response to multiple cardiovascular disorders, such as acute myocardial infarction (AMI), ischemic cardiomyopathy, dilated hypertensive heart disease, inflammatory diabetic and aortic stenosis. Fibrotic remodeling mainly sustained by differentiation of fibroblasts into myofibroblasts, which synthesize secrete most extracellular matrix (ECM) proteins. An increase intracellular Ca2+ concentration ([Ca2+]i) cardiac emerging critical mediator fibrogenic signaling cascade. Herein, we review mechanisms may shape signals involved fibroblast transdifferentiation myofibroblasts. We focus our attention on functional interplay between inositol-1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) store-operated entry (SOCE). In accordance with this, InsP3Rs SOCE drive elicited Gq-protein coupled (GqPCRs) promote fibrotic remodeling. Then, describe additional sustain entry, including receptor-operated (ROCE), P2X receptors, Transient Receptor Potential (TRP) channels, Piezo1 channels. parallel, discuss pharmacological manipulation handling machinery promising approach mitigate or reverse disorders.

Language: Английский

Citations

0
High-fidelity spatio-temporal recognition of mitochondrial esterase with an on-demand photoactivation strategy DOI
Lixin Sun, Huili Liu, Zehua Qian

et al.

Science China Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

0
Mitophagy in Alzheimer's disease and other metabolic disorders: a focus on mitochondrial-targeted therapeutics DOI

Shadt Skawratananond,

Daniel X Xiong,

Charlie Zhang

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102732 - 102732

Published: March 1, 2025

Language: Английский

Citations

0
TP53INP2 promotes mitophagic degradation of YAP to impede dedifferentiated liposarcoma development DOI
Yixuan Wang, Ying Huang, Liwei Wang

et al.

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

Published: April 4, 2025

Language: Английский

Citations

0
Is There a Mitochondrial Protection via Remote Ischemic Conditioning in Settings of Anticancer Therapy Cardiotoxicity? DOI Creative Commons
Petra Kleinbongard, Ioanna Andreadou

Current Heart Failure Reports, Journal Year: 2024, Volume and Issue: 21(4), P. 292 - 304

Published: March 21, 2024

Abstract Purpose of Review To provide an overview (a) protective effects on mitochondria induced by remote ischemic conditioning (RIC) and (b) mitochondrial damage caused anticancer therapy. We then discuss the available results studies protection via RIC in therapy-induced cardiotoxicity. Recent Findings In three experimental healthy mice pigs, there was a RIC-mediated against anthracycline-induced cardiotoxicity some evidence improved function with RIC. The not confirmed two cancer patients. adult patients, associated adverse outcome. There are no data Summary Studies tumor-bearing animals needed to determine whether does interfere properties drugs actually improves function, ultimately resulting cardiac function.

Language: Английский

Citations

3
The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure DOI Creative Commons

Anna De Bartolo,

Teresa Pasqua,

Naomi Romeo

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 20, 2024

Abstract Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute protection. However, its action in chronic settings dysfunction is not understood. Here, we investigated role SELENOT pathophysiology HF: (i) by designing small peptide (PSELT), recapitulating activity via redox site, assessed beneficial preclinical model HF [aged spontaneously hypertensive (SHHF) rats] against isoproterenol (ISO)-induced ventricular H9c2 adult human AC16 cardiomyocytes; (ii) evaluating intra-cardiomyocyte production secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, severe ultrastructural alterations, while counteracting mediators fibrosis, aging, DNA damage restoring desmin downregulation upregulation failing hearts. In hemodynamic assessment, improved contractile impairment at baseline following ischemia/reperfusion reduced infarct size normal At cellular level, counteracted ISO-mediated alterations through motif, mitigating ISO-triggered intracellular secretion, phenomenon presumably reflects extent cell damage. Altogether, these results indicate could represent novel sensor cardiomyocytes potential PSELT-based new therapeutic approach HF. Graphical

Language: Английский

Citations

3
BET inhibitors (BETi) influence oxidative phosphorylation metabolism by affecting mitochondrial dynamics leading to alterations in apoptotic pathways in triple‐negative breast cancer (TNBC) cells DOI Creative Commons
Teresa Rossi, Egidio Iorio, Mattea Chirico

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(12)

Published: Sept. 2, 2024

Repressing BET proteins' function using bromodomain inhibitors (BETi) has been shown to elicit antitumor effects by regulating the transcription of genes downstream BRD4. We previously showed that BETi promoted cell death triple-negative breast cancer (TNBC) cells. Here, we proved induce altered mitochondrial dynamics fitness in TNBC cells falling death. demonstrated treatment downregulated expression BCL-2, and proteins involved fission increased fused mitochondria. Impaired affected oxidative phosphorylation (OXPHOS) inducing OXPHOS-related genes, SDHa ATP5a, Consistently, amount DNA membrane potential (∆Ψm) BETi-treated compared control Lastly, combination with Metformin reduced growth. Our results indicate OXPHOS metabolism support proliferation represent novel targets

Language: Английский

Citations

2
A Review of Advances in Mitochondrial Research in Cancer DOI Creative Commons
Zhiru Li, Wu Zhang,

Shaowei Guo

et al.

Cancer Control, Journal Year: 2024, Volume and Issue: 31

Published: Jan. 1, 2024

Abnormalities in mitochondrial structure or function are closely related to the development of malignant tumors. Mitochondrial metabolic reprogramming provides precursor substances and energy for vital activities tumor cells, so that cancer cells can rapidly adapt unfavorable environment hypoxia nutrient deficiency. Mitochondria enable gain ability proliferate, escape immune responses, develop drug resistance by altering constitutive junctions, oxidative phosphorylation, stress, subcellular relocalization. This greatly reduces rate effective clinical control

Language: Английский

Citations

2
Mechanisms of Myocardial Edema Development in CVD Pathophysiology DOI Creative Commons
Diana G. Kiseleva, Tatiana V. Kirichenko, Yuliya V. Markina

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 465 - 465

Published: Feb. 19, 2024

Myocardial edema is the excess accumulation of fluid in myocardial interstitium or cardiac cells that develops due to changes capillary permeability, loss glycocalyx charge, imbalance lymphatic drainage, a combination these factors. Today it believed this condition not only complication cardiovascular diseases, but itself causes aggravation disease and increases risks adverse outcomes. The study molecular, genetic, mechanical myocardium during may contribute development new approaches diagnosis treatment condition. This review was conducted describe main mechanisms at molecular cellular levels identify promising targets for regulation based on articles cited Pubmed up January 2024.

Language: Английский

Citations

1