Abstract
BackgroundThe composition and function of the adipose tissue covering the heart are poorly known. In this study, we have investigated the epicardial adipose tissue (EAT) covering the cardiac ventricular muscle and the EAT covering the left anterior descending artery (LAD) on the human heart, to identify their resident stem cell functional activity.MethodsEAT covering the cardiac ventricular muscle was isolated from the apex (avoiding areas irrigated by major vessels) of the heart (ventricular myocardium adipose tissue (VMAT)) and from the area covering the epicardial arterial sulcus of the LAD (PVAT) in human hearts excised during heart transplant surgery. Adipose stem cells (ASCs) from both adipose tissue depots were immediately isolated and phenotypically characterized by flow cytometry. The different behavior of these ASCs and their released secretome microvesicles (MVs) were investigated by molecular and cellular analysis.ResultsASCs from both VMAT (mASCs) and the PVAT (pASCs) were characterized by the expression of CD105, CD44, CD29, CD90, and CD73. The angiogenic-related genes VEGFA, COL18A1, and TF, as well as the miRNA126-3p and miRNA145-5p, were analyzed in both ASC types. Both ASCs were functionally able to form tube-like structures in three-dimensional basement membrane substrates. Interestingly, pASCs showed a higher level of expression of VEGFA and reduced level of COL18A1 than mASCs. Furthermore, MVs released by mASCs significantly induced human microvascular endothelial cell migration.ConclusionOur study indicates for the first time that the resident ASCs in human epicardial adipose tissue display a depot-specific angiogenic function. Additionally, we have demonstrated that resident stem cells are able to regulate microvascular endothelial cell function by the release of MVs.
Highlights
The composition and function of the adipose tissue covering the heart are poorly known
Proliferation and viability of Adipose-derived stem cells (ASCs) from the different adipose tissue depots The proliferative rate of ASCs obtained from VMAT was always higher than that of ASCs obtained from Perivascular adipose tissue (PVAT) (Fig. 2b); the main change was observed during the first 4 days; the calculated doubling time of Ventricular myocardium adipose stem cells (mASCs) and Perivascular adipose stem cells (pASCs) was almost the same during days 6 and 8 (Fig. 2c)
We found that pASCs express a higher amount of VEGFA, as well as a reduced expression of COL18A1, compared with the mASCs, suggesting a coordinated regulation of angiogenesis through these two proteins by epicardial adipose tissue (EAT)-derived ASCs, which is increased on pASC, in direct contact with the left anterior descending artery (LAD) compared with mASC
Summary
The composition and function of the adipose tissue covering the heart are poorly known. Lambert et al Stem Cell Research & Therapy (2019) 10:361 of angiogenic factors, and have immunomodulatory properties. All these properties have encouraged its use to induce ischemic tissue recovery. Their clinical use of bone marrow stem cells has been hampered by the recognition of the loss of function effects of aging, cardiovascular risk factors (CVRFs), and metabolic disorders [8]. Regarding spontaneous endogenous repair, our group has shown that the presence of CVRFs, such as type 2 diabetes mellitus, negatively affects the pluripotency and self-renewal capacities of adipose stem cells (ASCs) [9], and ASCs obtained from obese patients display an impaired angiogenic potential [10, 11]. The spontaneous regenerative capacity for ASC self-renewal seems to be regulated by the anatomical WAT depot
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