## 3 Results
### Cardiac LyV Density and Structural Remodeling  
The density of LyVs expressed as the ratio of the LyV number to the number of cardiomyocytes in the left ventricular and IVS myocardium was diminished in the db/db and Ang II-treated db/db mic, compared to this ratio in the wild-type animals (Figure 7A,C). Of note, the density of LyVs in the control mice receiving Ang II was higher than that in the Ang II-treated db/db mice and almost equal to the density in the control animals in the RV (Figure 7B). Furthermore, the density of LyVs in subepicardial and pericoronary areas was almost the same among the four groups (Figure 7D,E), in contrast to the diminished density of LyVs in intramyocardial regions in the db/db and Ang II-treated db/db mice compared to the control (Figure 7F). Occasionally, LECs with morphological signs of injury were observed in the db/db and db/db mice treated with Ang II (Supplementary Figure S3). Figure 5: Inflammatory cell density in the LV of the control, Ang II-treated control, db/db, and Ang II-treated db/db mice assessed by the number of CD45\({}^{+}\)/CD68\({}^{+}\) and CD68-positive cells per mm\({}^{2}\) of cardiac tissue in at least three cardiac tissue sections from all the experimental groups. Measurements were taken in areas devoid of scars and of pericoronary locations on tissue cross-sectioned in the middle part of the heart at the midlevel between the base and the apex; statistical analysis was performed between each of two groups by Student’s \(t\)-test with [PERSON]’s correction; \({}^{*}p<0.05\), \({}^{**}p<0.002\); number of tile scan sections from each study group = 3; n = 20–40 number of measurements taken on every entire tile scan section. The confocal microscopic images did not present marked differences in the LyV shapes and structures among the groups. The structural abnormalities in the cardiac LyVs in the experimental mice were rather subtle. In the db/db mice, odd-shaped vessels in myocardial locations were seen compared to the shapes of the LyVs in the control animals. Importantly, in the Ang II-treated control and db/db mice, LyVs positioned in pericoronary locations were partially embedded in a thickened fibrous tissue of adventitia and were mostly of oval shapes (Figure 8B,D). TEM analyses revealed details of the altered LyV wall shapes in the Ang II-treated control (Figure 9B,B\({}^{\prime}\)) and db/db mice (Figure 9C,C\({}^{\prime}\)) compared with the controls and with the contr + Ang II mice (Figure 9A,A\({}^{\prime}\)). The vessel walls in the myocardium of the db/db animals and in both Ang II-treated groups were wavy and undulating, in contrast to those observed in the control mice (Figure 9C vs. Figure 9A). Moreover, in the Ang II-treated db/db mice, long cytoplasmic processes protruding toward the vessel lumina were often visible (Figure 9D,D\({}^{\prime}\)). In addition, the overlapping flaps of the LECs were altered in the experimental groups vs. control, i.e., the flaps were often long and wavy, especially those projecting into the vessel lumen (Supplementary Figure S4B-D, vs. Figure S4A). The intercellular junctions of these flaps had larger gaps compared to those in the control mice (Supplementary Figure S4A vs. Figures S4B-D and 10A). Figure 6: Interstitial fibrosis presented in the outer half (**A**–**E**), and inner half of the left ventricular wall (**F**–**J**). (**A,F**)—graphs showing the percentage of collagen deposits per total measured myocardial areas in all the experimental groups in the epicardial half (epi-) and the endocardial half (endo-) of the myocardial wall, respectively. Measurements were performed in areas without scars and without pericoronary fibrosis. Statistics—\({}^{*}p<0.05\), \({}^{**}p<0.02\), \({}^{***}p<0.0002\), \({}^{***}p<0.0001\); number of tissue sections from each study group = 3; number of measurements: on average, 20 from every tissue section.