Role of Chitinase-3-like Protein 1 in Cardioprotection and Angiogenesis by Post-Infarction Exercise Training.
Zhuo LiFangnan WuLei XiZhenjun TianPublished in: Biomedicines (2022)
Chitinase-3-like protein 1 (CHI3L1) is a myokine involving tissue remodeling and inflammatory processes. CHI3L1 and its receptor protease-activated receptor 2 (PAR2) are induced by exercise in skeletal muscles. However, it remains unknown if CHI3L1/PAR2 signaling also mediates exercise-induced cardioprotection after myocardial infarction. Twenty-four adult male rats were divided into three groups (n = 8/group), receiving: (1) a sham operation; (2) permanent ligation of left anterior descending coronary artery; and (3) post-MI exercise training with one-week adaptive treadmill exercise for seven days followed by four weeks of aerobic exercise. Left ventricular systolic and end-diastolic pressure indices were measured and cardiac fibrosis, and angiogenesis were examined. Furthermore, HUVEC cells were treated in vitro with AMPK agonist-AICAR (a putative pharmacological memetic of exercise), recombinant human CHI3L1, PAR2 receptor blocker (AZ3451), and PI3K inhibitor (LY294002), respectively. We found that post-MI exercise significantly upregulated CHI3L1, PAR2, pPI3K/PI3K, pAKT/AKT, pERK/ERK, improved cardiac function, and diminished fibrosis. AICAR increased HUVEC tubules formation and upregulated CHI3L1 and PAR2 and these changes were attenuated by PAR2 blocker. In conclusion, post-MI exercise training can effectively activate CHI3L1/PAR2 signaling, which led to the improved myocardial function and enhanced cardiac angiogenesis in the infarcted heart.
Keyphrases
- left ventricular
- high intensity
- skeletal muscle
- coronary artery
- heart failure
- physical activity
- endothelial cells
- vascular endothelial growth factor
- recombinant human
- blood pressure
- acute myocardial infarction
- cell proliferation
- signaling pathway
- cardiac resynchronization therapy
- resistance training
- induced apoptosis
- left atrial
- wound healing
- randomized controlled trial
- endoplasmic reticulum stress
- clinical trial
- small molecule
- oxidative stress
- newly diagnosed
- pulmonary artery
- angiotensin converting enzyme
- cell cycle arrest
- percutaneous coronary intervention
- protein protein
- ejection fraction