Increased pulmonary expression of P2Y6 receptor and right ventricle hypertrophy in a COPD murine model

<bold>Background:</bold> Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide due to multisystemic damage, where lung damage is characterized by emphysema and remodeling in airway and pulmonary vasculature, with functional impairment and associated pulmonary hypertension. Purinergic P2Y6 receptor has been involved in fibrosis and vasoconstriction, however there is scarce evidence about P2Y6 receptor in COPD and secondary pulmonary hypertension. Therefore, we aimed to determine P2Y6 gene expression and right ventricle hypertrophy (RVH) in a murine model of COPD induced by cigarette smoke (CS). <bold>Methods:</bold> Sixteen A/J mice, female, 10 weeks old, were exposed to CS (n=8) or room air (n=8) for 6 months, 5 days/week, 1 time/day, 1 hour/session using 12 cigarettes to induce COPD (protocol approved by institutional Ethics Committee). Lungs and hearts were collected for qRT-PCR, Fulton Index (FI), right ventricle weight and heart length normalized by tibia length, after emphysema confirmation. Parametric and nonparametric analysis were performed. <bold>Results:</bold> Increase was observed in P2Y6 mRNA levels in lungs of CS (41.62±16.29-fold increase) (p=0.0213), in RV weight in CS (0.02, IR 0.016-0.024 g/cm) (p=0.0303), and heart length in CS (0.49±0.025 cm/cm) (p=0.0127) v/s control group, with FI >0.34 in 6/7 mice, indicating RVH. We observed a reduction in collagen 1a1 mRNA levels in lungs of CS (0.54±0.25) (p=0.0468), with no significant changes in alpha-SMA mRNA levels. <bold>Conclusion:</bold> P2Y6 gene expression was induced in COPD with associated RV hypertrophy, suggesting that P2Y6 receptor could be involved in mechanisms of COPD and secondary pulmonary hypertension.