Abstract
Myocardial infarction (MI), atherosclerosis and other inflammatory and ischemic cardiovascular diseases (CVDs) have a very high mortality rate and limited therapeutic options. Although the diagnosis is based on markers such as cardiac Troponin-T (cTrop-T), the mechanism of cTrop-T upregulation and release is relatively obscure. In the present study, we have investigated the mechanism of cTrop-T release during acute hypoxia (AH) in a mice model by ELISA & immunohistochemistry. Our study showed that AH exposure significantly induces the expression and release of sterile inflammatory as well as MI markers in a time-dependent manner. We further demonstrated that activation of TLR3 (mediated by eRNA) by AH exposure in mice induced cTrop-T release and Poly I:C (TLR3 agonist) also induced cTrop-T release, but the pre-treatment of TLR3 immuno-neutralizing antibody or silencing of Tlr3 gene or RNaseA treatment two hrs before AH exposure, significantly abrogated AH-induced Caspase 3 activity as well as cTrop-T release. Our immunohistochemistry and Masson Trichrome (MT) staining studies further established the progression of myocardial injury by collagen accumulation, endothelial cell and leukocyte activation and adhesion in myocardial tissue which was abrogated significantly by pre-treatment of RNaseA 2 hrs before AH exposure. These data indicate that AH induced cTrop-T release is mediated via the eRNA-TLR3-Caspase 3 pathway.
Highlights
Ascent to high altitudes generates a hypoxic environment in the body, causing hypoxemia in the circulation that leads to inflammation and hypercoagulation [1]
The mice that were subjected to acute hypoxia (AH) exposure showed significantly higher levels of sterile inflammation (SI) markers i.e., HMGB1, vWF, HSPs, s100b, Extracellular RNA (eRNA) and eDNA (Fig 1A– 1G; p < 0.05)
This study explored the mechanism of myocardial injury due to exposure of AH
Summary
Ascent to high altitudes generates a hypoxic environment in the body, causing hypoxemia in the circulation that leads to inflammation and hypercoagulation [1]. Several disorders such as CVDs, pulmonary and cerebral edema are concomitant with hypoxia-induced inflammation [2]. The fundamental cause of morbidity and mortality in MI [3] and acute lung injury [4] has been observed to be vascular inflammation due to hypoxia. Traditional diagnostic checks for AMI include an onset of chest pain and abnormalities in electrocardiographic (ECG) tests.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
