Perirenal Adipose Tissue in Cardiovascular Disease: From Molecular Insights to Therapeutic Perspectives

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  Figure 1. The morphological architecture of PRAT. PRAT is a visceral adipose tissue depot located around the kidneys. In adults, PRAT is primarily composed of white and brown adipocytes, which can be identified by their specific molecular markers. PRAT adipocytes are derived from ADMSCs, which express CD90 and CD166 but lack the expression of CD31 and CD45. In obesity, PRAT undergoes a brown-to-white adipocyte transition, accompanied by the appearance of beige adipocytes expressing markers such as Tbx1, CD137, Epsti1, and Tmem26. Overall, PRAT contains a relatively high proportion of dormant brown adipocytes, is richly innervated by sympathetic nerves, exhibits high levels of saturated free fatty acids, and plays an important role in the cardio–renal–metabolic axis. ACOT11—acyl-CoA thioesterase 11; ADMSCs—adipose-derived mesenchymal stem cells; C/EBP α—CCAAT-enhancer-binding protein α; CIDEA—cell death-inducing DFFA-like effector a; CD—cluster of differentiation; CLSTN3—calsyntenin-3; Epstil1—epithelial stromal interaction 1; FABP—fatty acid-binding protein; HOX—homeobox; PPARɣ—peroxisome proliferator-activated receptor ɣ; PRAT—perirenal adipose tissue; SPARC—secreted protein, acidic, and…

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  Figure 2. Potential mechanisms of PRAT involvement in atherosclerotic cardiovascular disease. Endothelial dysfunction is promoted by an imbalance in the secretory profile of PRAT, characterized by enhanced leptin production accompanied by reduced levels of protective adipokines, including omentin and irisin. In addition, mitochondrial dysfunction in PRAT adipocytes enhances ROS generation, thereby contributing to oxidative stress and vascular-wall inflammation. The proliferation of vascular smooth muscle cells (VSMCs) is further stimulated by increased leptin and CTRP levels, promoting vascular remodelling. Pro-inflammatory cytokines, particularly TNF-α and IL-6, exacerbate lipolysis and facilitate immune-cell infiltration into PRAT, especially by macrophages, thereby supporting local and systemic inflammation. Furthermore, increased levels of oxLDL, together with reduced PRAT-derived adiponectin, vaspin, and asprosin, promote macrophage foam-cell formation within the vascular wall, accelerating the initiation and progression of atherosclerotic plaque development. ACAT-1—acetyl-coenzyme A acetyltransferase 1; CTRPs—C1q/TNF-related proteins; CYP1B1—cytochrome P450 1B1 enzyme; GLUT4—glucose…

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  Figure 3. Potential mechanisms of PRAT in hypertension. Endothelial dysfunction may result from increased secretion of PRAT-derived leptin and TNF-α, as well as from the direct mechanical compression of the renal parenchyma by excessive PRAT. Leptin further contributes to vascular dysfunction by promoting vasoconstriction and activation of the renin–angiotensin–aldosterone system (RAAS), whereas activation of renal afferent sensory nerves within PRAT enhances renal sympathetic nerve activity, leading to sustained elevated blood pressure. Concurrently, reduced adiponectin secretion of PRAT promotes renal sodium and glucose reabsorption via increased sodium–glucose cotransporter 2 (SGLT2) activity. These effects are further amplified by the upregulation of miR-802, miR-146a, and miR-155, which contribute to increased vascular tone, renal fibrosis, and hypertension. CGRP—calcitonin gene-related peptide; eNOS—endothelial nitric oxide synthase; HIF-1 α—hypoxia-inducible factor 1 α; miR—microRNA; Mpv17l–mitochondrial inner membrane protein-like 17l; NLRP3—NOD-like receptor protein 3; NO—nitric oxide; NRF—NF-κB repressing factor; PRAT—perirenal adipose tissue; RAAS—renin–angiotensin–aldosterone…

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  Figure 4. Potential PRAT-based therapies in cardiovascular diseases. Colchicine and BMP4 administration, together with modulation of the gut microbiota, adipose-derived mesenchymal stem-cell (ADMSC)-based approaches, and senolytic therapies, is an emerging therapeutic strategy for cardiovascular disease prevention in obese patients through targeted modulation of PRAT. Moreover, advanced image analysis using machine learning algorithms may further improve cardiovascular risk stratification in these patients. ADMSC–adipose-derived mesenchymal stem cell; BMP4–bone morphogenetic protein 4.