Pentraxin 3 depletion (PTX3 KD) inhibited myocardial fibrosis in heart failure after myocardial infarction

Abstract

Background: HF is a common complication of MI. The underlying mechanisms of myocardial fibrosis in HF after MI are incompletely defined. Here, this study aims to investigate the role of PTX3 KD in HF after MI. Methods: Bioinformatics analysis based on GSE86569 dataset was performed to explore the potential role of PTX3 in HF. Male C57/BL6J mice were administered with lentiviral vector encoding PTX3 KD or empty vector, and then underwent either coronary ligation or sham surgery. Echocardiography, Masson staining, and immunofluorescence counterstaining were conducted to evaluate the cardiac function and fibrosis. Cardiac fibroblasts were isolated and transfected with lentiviral vector encoding PTX3 KD in vitro to verify the in vivo findings. Results: Bioinformatics analysis based on GSE86569 revealed the aberrant expression of PTX3 in HF patients. Echocardiography showed that PTX3 KD reversed the HF-induced cardiac dysfunction with better cardiac function parameters. Masson staining demonstrated that the obvious infarct and high fibrosis ratio in HF mice were remarkably improved after PTX3 KD. Immunofluorescence staining indicated that the HF-induced increase expression of α-SMA was significantly suppressed by PTX3 KD. Additionally, both in vivo and in vitro results confirmed that PTX3 KD decreased the fibrosis-related up-regulation of collagen I, collagen III, and p-STAT3. However, the result was opposite after IL-6 treatment. Conclusions: PTX3 KD protects the cardiac function and counteracts the myocardial fibrosis by down-regulating IL-6/STAT3 pathway in HF.

miR-135a Mediates Mitochondrial Oxidative Respiratory Function through SIRT1 to Regulate Atrial Fibrosis

“…These findings reveal MF is associated with collagen metabolism and contributes in the mechanism of AF. The clinical data showed that many factors are associated with the process of MF, such as oxidative stress, calcium overload, inflammation, and the activation of myofibroblasts [1][2][3]. In normal conditions, the body can produce antioxidant enzymes such as SOD to remove excess ROS and keep the level of free radicals in the body at a steady state [23].…”

“…Persistent atrial fibrillation (AF) can lead to electrical and structural remodeling, and myocardial fibrosis (MF) is an important feature of structural remodeling. Available experimental and clinical data suggest that there are many factors involving in the development of MF and AF, such as calcium overload, inflammation, oxidative stress, and activation of myofibroblasts [1][2][3]. MF is an important pathological feature of AF, resulting in the excessive deposition of the extracellular matrix, causing myocardial remodeling and even heart failure (HF) [4,5].…”

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

“…Moreover, There are many other drugs that can improve fibrosis, such as piperine, thymoquinone, an oleanolic acid Qi-Tai-Suan, spinal cord stimulation and exogenous hydrogen sulfide ( Li et al, 2020f ; Viswanadha et al, 2020 ; Farag et al, 2021 ; Qian et al, 2022 ; He et al, 2023 ). Endostatin, alarin, L-carnitine, pentraxin 3 depletion, and mdivi-1 also can attenuate oxidative stress to inhibit myocardial fibrosis ( Li et al, 2021b ; Xu et al, 2021b ; Emran et al, 2021 ; Xu et al, 2022a ; Ding et al, 2022 ).…”