The effect of microvascular remodeling on fluid dynamics in the pressure-overloaded right ventricle

Right ventricular (RV) failure, a major complication of pulmonary hypertension, is preceded by myocardial remodeling, yet the contribution of the microvasculature remains unclear. Previous two-dimensional (2-D) studies provided critical insight into microvascular remodeling in the stressed myocardium, but our work shows that this process unfolds in three dimensions (3-D). Here, we combine advanced 3-D imaging with computational fluid dynamics (CFD) to quantify how microvascular remodeling alters hemodynamic parameters-specifically wall shear stress (WSS) and microvascular resistance-in the pressure-overloaded RV. Using male and female mice at 4 and 7 weeks after pulmonary artery banding (PAB), we reconstructed 3-D models of the coronary microcirculation for morphological analyses and CFD simulations. Samples from SHAM (<i>N</i>_female/<i>N</i>_male = 6/5), PAB-4 wk (6/8), and PAB-7 wk (5/5) groups were analyzed using deep tissue confocal imaging. A linear mixed-effects model accounted for within- and between-mouse variability in hypothesis testing. Compared with SHAM, PAB mice exhibited marked structural alterations in the right coronary microvasculature, including increased tortuosity, reduced segment length, and enlarged capillary radii, which collectively lowered microvascular resistance and WSS. Sex-based differences were evident mainly in SHAM mice; no clear sex-specific response to PAB was observed except for hemodynamic resistance, which was higher in healthy males but declined only in male PAB mice to levels comparable to SHAM females. These findings suggest that microvascular remodeling in the pressure-overloaded RV reduces hemodynamic resistance and WSS, indicating a potentially adaptive response.<b>NEW & NOTEWORTHY</b> This study reveals that microvascular remodeling in the pressure-overloaded right ventricle (RV) leads to reduced microvascular resistance and wall shear stress, potentially supporting coronary perfusion. Using 3-D imaging and computational fluid dynamics, we demonstrate increased vessel tortuosity, shorter capillary segments, and larger radii, contributing to hemodynamic adaptation. Sex-based differences were observed at baseline, but both sexes exhibited similar remodeling responses post overload. These findings highlight adaptive microvascular changes that may influence RV function under chronic stress.