## 1 Introduction  
Although the cardiac lymphatic system has received increasing attention during the past decade, little is known about its structural remodeling in the disease states, especially in obesity, which nowadays has become a pandemic. In addition, obese individuals are often affected by hypertension, hyperglycemia/type 2 diabetes (T2 DM) and dyslipidemia, which together define metabolic syndrome (MetS) [1; 2; 3; 4]. Each of these factors, acting individually or together, may contribute to cardiac LyV dysfunction and rarefaction. The effects of these factors have been examined extensively on extracardiac lymphatic vessels, as summarized before [5]. Disruption of LyV integrity and impaired lymphangiogenesis have been reported in mice models of obesity and T2 DM [6; 7; 8; 9], and in obesity alone [10; 11; 12]. Ang II, a component of the renal and tissue renin-angiotensin system, upon infusion to animals, leads to an increased arterial blood pressure, cardiac remodeling [13; 14], and enhanced lymphangiogenesis, with LyV hyperpermeability in the heart tissue of individuals without metabolic disorders [15; 16]. However, it remains unclear what effect Ang II exposure has on cardiac LyVs in obese individuals. The architecture of the cardiac lymphatic system and the basis of its functioning are described in several review articles [17; 18; 19; 20; 21]. Shortly, interstitial fluid with solutes and inflammatory cells in the heart is absorbed by blind-ended initial capillaries where lymph is formed [22]. These capillaries are located within the subepicardial area and in the outer half of the myocardial wall in the mouse heart (as shown in schematic Figure 1A,B) and successively propel the lymph into precollectors, which are situated in the subepicardial area, and further into collectors located outside the heart [23; 24]. After passing through the mediastinal lymph nodes, the lymph is drained into the venous system via the thoracic duct and the right lymphatic duct [24; 25]. The initial capillaries are composed of a single layer of oak leaf-shaped lymphatic endothelial cells (LECs), which form the primary valve system created by loosely overlapping flaps of adjacent LECs interconnected by button-like junctions to ensure the structural integrity of the LyV wall. The primary valve system regulates the en  
Figure 1: **(A)** Schematic presentation of the LyV location within cardiac compartments in mice; the subepicardial LyVs are marked with yellow-edged arrows, pericoronary LyVs are marked with blue-edged arrows, and intramyocardial LyVs are marked with violet-edged arrows, LyVs are marked with red lines (ovals/circles), coronary artery is marked with the white-edged arrow. **(B)** Areas selected for calculations of the cardiac LyV number per number of cardiomyocytes; the left ventricular area containing LyVs is encircled with the white line, the IVS area is encircled with the green line, the right ventricular area is encircled with the yellow line. **(C)** Areas selected for counting the subepicardially located LyVs: encircled with the white line—the subepicardium of the LV, encircled with the yellow line—the subepicardium of the RV. Scale bar—0.9 mm. and immune cells between the LECs (paracellular route of transport) and prevents backflow movement of the lymph to the interstitium [26; 27; 28]. Alternatively, fluid and solute transport from the extracellular space to the lumen of the LyV occurs via cytoplasmic vesicles (transcellular transport) in the LECs [29; 30]. Dysregulated transport via the LyV wall at the level of initials is described as lymph leakage. The morphological features of leakage from initials in the myocardium remain unknown, although leaky LyVs in extracardiac locations have been reported in obesity [31; 32; 33], T2 DM [6] and hypercholesterolemiaaemia [34]. The abluminal cytoplasmic membrane of the LECs is connected with the extracellular matrix (ECM) via anchoring filaments (AnchFs). It has been reported that degradation of AnchFs impedes lymphatic drainage [35; 36; 37].