Lymphatic vessel remodeling in the hearts of Ang II-treated obese db/db mice as an integral component of cardiac remodeling

Cardiac lymphatic vessels (LyVs) are suggested to be important players in cardiovascular disease-associated myocardial remodeling. However, there is a gap in the knowledge of whether LyV remodeling is an integral component of cardiac remodeling, especially in obesity associated with other comorbidities, including increased levels of circulating angiotensin II (Ang II). We studied the structural alterations in the myocardium and LyVs in Ang II-treated db/db mice compared with db/db mice and Ang II-treated wild-type mice with histopathological imaging methods, confocal microscopy, ultrastructural morphology, and morphometric analysis. We demonstrated that Ang II-treated db/db mice exhibited significantly increased fibrosis, cardiomyocyte hypertrophy, and local edema compared with untreated db/db mice; however, the cardiomyocyte hypertrophy was similar to that in Ang II-treated control mice. The decreased density of the LyVs and their wall shape alterations, with disorganized anchoring filaments, widened junctional gaps, decreased numbers of cytoplasmic vesicles indicative of a leaky phenotype, and increased basement membrane (BM) thickness, were observed in Ang II-treated db/db mice compared with Ang II-treated controls. Our findings revealed a structural basis for intensive LyV remodeling in association with cardiac remodeling in obesity.