In Vitro Assessment of Cardiac Fibroblast Activation at Physiologic Stiffness DOI Creative Commons
Robert Goldsmith,

Yao‐Chang Tsan,

Rachel E. Scissors

et al.

Current Protocols, Journal Year: 2024, Volume and Issue: 4(4)

Published: April 1, 2024

Abstract Cardiac fibroblasts (CF) are an essential cell type in cardiac physiology, playing diverse roles maintaining structural integrity, extracellular matrix (ECM) synthesis, and tissue repair. Under normal conditions, these cells reside the interstitium a quiescent state poised to sense respond injury by synthesizing secreting collagen, vimentin, hyaluronan, other ECM components. In response mechanical chemical stimuli, “resident” can undergo transformation through continuum of activation states into what is commonly known as “myofibroblast,” process critical for response. Despite progress understanding contribution health disease, much remains unknown about signaling mediating this activation, part owing technical challenges evaluating CF function status vitro . Given their role monitoring ECM, CFs acutely sensitive stiffness pressure. High basal isolated common due super‐physiologic traditional culture substrates, making assays dependent on challenging. To overcome problem, parameters must be tightly controlled, use dishes coated with biocompatible reduced‐stiffness such 8‐kPa polydimethylsiloxane (PDMS), has shown promise reducing fibroblasts. Here, we describe protocol quiescence enable dynamic range assessment fibrogenic stimuli using PDMS‐coated coverslips. Our provides cost‐effective tool study fibroblast activity, allowing researchers better understand underlying mechanisms involved fibrosis. © 2024 The Authors. Current Protocols published Wiley Periodicals LLC. Basic Protocol 1 : Generation (PDMS)/gelatin‐coated coverslips 2 Isolation adult plating onto PDMS 3 Assessment α smooth muscle actin (αSMA) immunocytochemistry

Language: Английский

Biochanin A inhibits cardiac hypertrophy and fibrosis in vivo and in vitro DOI Open Access
Zhenyu Feng, Ningning Zhang, Jie Bai

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116002 - 116002

Published: Dec. 12, 2023

The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged stimulation, leading cardiomyocyte hypertrophy, fibroblast proliferation, and increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of myocardial remodeling. Biochanin A (BCA) is a kind flavonoid structural monomer, which has certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria other pharmacological properties. It still unknown whether BCA impact mechanism TAC-induced hypertrophy. Here, remodeling was induced by TAC. injected intraperitoneally at 25 50 mg/kg/day one week advance. Masson, WGA, DHE staining serum were used detect inhibitory mice. anti-hypertrophic demonstrated studying manifestations Neonatal rat cardiomyocytes (NRCMs) fibroblasts (CFs) vitro. results showed that significantly reduced fibrosis, inflammation, oxidative stress, inhibited Ang II-induced cell stress NRCMs vitro CF migration, collagen secretion. This suggests plays key role inhibiting progression remodeling, suggesting may be promising agent fibrosis.

Language: Английский

Citations

6
Effect of Extracellular Matrix Stiffness on Candesartan Efficacy in Anti-Fibrosis and Antioxidation DOI Creative Commons
Tong Zhu,

Jingjing Song,

Bin Gao

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 679 - 679

Published: March 9, 2023

Myocardial fibrosis progression and imbalanced redox state are closely associated with increased extracellular matrix (ECM) stiffness. Candesartan (CAN), an angiotensin II (Ang II) receptor inhibitor, has shown promising anti-fibrosis antioxidant efficacy in previous cardiovascular disease studies. However, the effect of ECM stiffness on CAN remains elusive. In this study, we constructed rat models three different degrees myocardial treated them CAN, then characterized stiffness, cardiac function, NADPH oxidase-2 (NOX2) expression tissues. Based obtained tissues, used polyacrylamide (PA) gels to mimic fibroblasts (CFs) at early, middle, late stages as cell culture substrates CFs mechanical microenvironment models. We studied effects PA gel migration, proliferation, activation without treatment, reactive oxygen species (ROS) glutathione (GSH) levels using fluorometry scanning electrochemical microscopy (SECM). found that best amelioration function NOX2 rats medium-stiffness tissue, most obvious gels. Our work proves antioxidants for first time, results demonstrate drug should also be considered treatment diseases.

Language: Английский

Citations

4
Using Omics to Identify Novel Therapeutic Targets in Heart Failure DOI
Christelle Lteif, Yimei Huang, Leonardo A. Guerra

et al.

Circulation Genomic and Precision Medicine, Journal Year: 2024, Volume and Issue: 17(3)

Published: May 20, 2024

Omics refers to the measurement and analysis of totality molecules or biological processes involved within an organism. Examples omics data include genomics, transcriptomics, epigenomics, proteomics, metabolomics, more. In this review, we present available literature reporting on heart failure that can inform development novel treatments innovative treatment strategies for disease. This includes polygenic risk scores improve prediction genomic potential multiomics more efficiently identify targets further study. We also discuss limitations omic analyses barriers must be overcome maximize utility these types studies. Finally, address current state field future opportunities using better personalize strategies.

Language: Английский

Citations

1
Interleukin(IL)-37 attenuates isoproterenol (ISO)-induced cardiac hypertrophy by suppressing JAK2/STAT3-signaling associated inflammation and oxidative stress DOI Creative Commons
Xiaohua Guo, Pengfei Wang,

Huiqing Wei

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113134 - 113134

Published: Sept. 17, 2024

Language: Английский

Citations

1
In Vitro Assessment of Cardiac Fibroblast Activation at Physiologic Stiffness DOI Creative Commons
Robert Goldsmith,

Yao‐Chang Tsan,

Rachel E. Scissors

et al.

Current Protocols, Journal Year: 2024, Volume and Issue: 4(4)

Published: April 1, 2024

Abstract Cardiac fibroblasts (CF) are an essential cell type in cardiac physiology, playing diverse roles maintaining structural integrity, extracellular matrix (ECM) synthesis, and tissue repair. Under normal conditions, these cells reside the interstitium a quiescent state poised to sense respond injury by synthesizing secreting collagen, vimentin, hyaluronan, other ECM components. In response mechanical chemical stimuli, “resident” can undergo transformation through continuum of activation states into what is commonly known as “myofibroblast,” process critical for response. Despite progress understanding contribution health disease, much remains unknown about signaling mediating this activation, part owing technical challenges evaluating CF function status vitro . Given their role monitoring ECM, CFs acutely sensitive stiffness pressure. High basal isolated common due super‐physiologic traditional culture substrates, making assays dependent on challenging. To overcome problem, parameters must be tightly controlled, use dishes coated with biocompatible reduced‐stiffness such 8‐kPa polydimethylsiloxane (PDMS), has shown promise reducing fibroblasts. Here, we describe protocol quiescence enable dynamic range assessment fibrogenic stimuli using PDMS‐coated coverslips. Our provides cost‐effective tool study fibroblast activity, allowing researchers better understand underlying mechanisms involved fibrosis. © 2024 The Authors. Current Protocols published Wiley Periodicals LLC. Basic Protocol 1 : Generation (PDMS)/gelatin‐coated coverslips 2 Isolation adult plating onto PDMS 3 Assessment α smooth muscle actin (αSMA) immunocytochemistry

Language: Английский

Citations

0