Abstract
Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH). We hypothesized that heart‐relevant microRNAs, that is myomiRs (miR‐1, miR‐133a, miR‐208, miR‐499) and miR‐214, can have a role in the right ventricle in the development of PAH. To mimic PAH, male Wistar rats were injected with monocrotaline (MCT, 60 mg/kg, s.c.); control group received vehicle. MCT rats were divided into two groups, based on the clinical presentation: MCT group terminated 4 weeks after MCT administration and prematurely terminated group (ptMCT) displaying signs of terminal disease. Myocardial damage genes and candidate microRNAs expressions were determined by RT‐qPCR. Reduced blood oxygen saturation, breathing disturbances, RV enlargement as well as elevated levels of markers of myocardial damage confirmed PH in MCT animals and were more pronounced in ptMCT. MyomiRs (miR‐1/miR‐133a/miR‐208a/miR‐499) were decreased and the expression of miR‐214 was increased only in ptMCT group (P < 0.05). The myomiRs negatively correlated with Fulton index as a measure of RV hypertrophy in MCT group (P < 0.05), whereas miR‐214 showed a positive correlation (P < 0.05). We conclude that the expression of determined microRNAs mirrored the disease severity and targeting their pathways might represent potential future therapeutic approach in PAH.
Highlights
Pulmonary arterial hypertension (PAH) is a rare and severe disease, defined by an elevation in mean pulmonary arterial pressure[1] caused by increased vasoconstriction, vascular remodelling, fibrosis and stiffening of the pulmonary vasculature
We found significantly suppressed right ventricular (RV) tissue levels of all tested myomiRs exclusively in the prematurely terminated MCT rats (ptMCT) group whereas these were stable in monocrotaline group (MCT)
The right ventricle is an essential point of interest in PAH as it is the major determinant of functional state and prognosis of the disease.[38]
Summary
Pulmonary arterial hypertension (PAH) is a rare and severe disease, defined by an elevation in mean pulmonary arterial pressure[1] caused by increased vasoconstriction, vascular remodelling, fibrosis and stiffening of the pulmonary vasculature. Alterations in muscle-specific microRNAs (myomiRs), that is miR-1, miR-133a, miR-208 and miR-499, have been found in diverse cardiac injuries[12,13] and, recently, myomiRs have been unveiled to be sensitive markers of sudden death from myocardial infarction.[14] Their role in RV pathology resulting from PAH can be anticipated. MiR-133a is highly expressed in the heart and plays a role in cardiogenesis and cardiac conductance.[13] It has antiapoptotic properties in cardiomyocytes[19] and represses myocardial fibrosis.[20]. MiR-208a regulates the expression of Myh7b/miR-499 and is needed for the up-regulation of Myh7/miR-208b and β-MHC in pathological setting This microRNA is considered to govern myofiber diversification, stress responsiveness of the heart and cardiac remodelling[22,25] and it is important for proper cardiac conduction.[26]. Based on a close relation of the above-mentioned miRNAs to cardiac injury and remodelling, we suppose that these microRNAs could have an impact on the overwhelmed right ventricle in experimental PH and they could possibly help clarify pathological mechanisms occurring in this organ
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
