Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice

• Published in: International journal of molecular sciences Vol. 24; no. 14; p. 11284
• Main Authors: Park, Do-Yang, Heo, Woon, Kang, Miran, Ahn, Taeyoung, Kim, DoHyeon, Choi, Ayeon, Birnbaumer, Lutz, Cho, Hyung-Ju, Kim, Joo Young
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2023; MDPI
• Subjects: Blood pressure; Cardiac function; Cardiovascular disease; Cell growth; chronic intermittent hypoxia; Endothelin; Heart; Heart enlargement; Hypertension; Hypoxia; Kinases; Lungs; Magnetic resonance imaging; Nitric oxide; obstructive sleep apnea; Pathology; Peptides; Pulmonary arteries; Pulmonary hypertension; right ventricle; right ventricle dilation; right ventricle hypertrophy; Sleep apnea; Sleep apnea syndromes; Smooth muscle; transient receptor potential cation channel 3; South Korea; obstructive sleep apnea; endothelin; right ventricle; right ventricle hypertrophy; chronic intermittent hypoxia; right ventricle dilation; transient receptor potential cation channel 3
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241411284

Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3 mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in mice without notable changes in pulmonary vasculature under CIH conditions.