Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation

Boucher, Joshua M.; Robich, Michael P.; Scott, Sadeaqua S; Yang, Xuehui; Ryzhova, Larisa; Turner, Jacqueline E.; Pinz, Ilka; Liaw, Lucy

doi:10.1007/s10557-018-6813-y

Cited by 13 publications

(10 citation statements)

References 58 publications

(76 reference statements)

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“…1A shows a schematic of the anatomical region where the PVAT overlying the ascending aorta was obtained. We previously described the patient populations undergoing coronary artery bypass grafting from which these samples were derived 6 . Fig.…”

Section: Representative Resultsmentioning

confidence: 99%

“…Using primary cultured human PVAT stromal vascular fraction, we tested three assays designed to induce stem/progenitor cells to differentiate toward adipogenic, osteogenic, or chondrogenic lineages. Our prior study identified a population of CD73+, CD105+, and PDGFRα+ (CD140a) cells that can robustly differentiate into adipocytes 6 , although their multipotency was not tested. PVAT directly regulates vascular tone and inflammation 7 .…”

Section: Introductionmentioning

confidence: 99%

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Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells

Scott

Yang

Robich

et al. 2019

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Adipose tissue is a rich source of multi-potent mesenchymal stem cells (MSC) capable of differentiating into osteogenic, adipogenic and chondrogenic lineages 1. Adipogenic differentiation of progenitor cells is a major mechanism driving adipose tissue expansion and dysfunction in response to obesity. Understanding changes to perivascular adipose tissue (PVAT) is thus clinically relevant in metabolic disease. However, previous studies have been predominately performed in the mouse and other animal models. This protocol uses human thoracic PVAT samples collected from patients undergoing coronary artery bypass graft surgery. Adipose tissue from the ascending aorta was collected and used for explantation of the stromal vascular fraction. We previously confirmed the presence of adipose progenitor cells in human PVAT with the capacity to differentiate into lipid-containing adipocytes. In this study, we further analyzed the differentiation potential of cells from the stromal vascular fraction, presumably containing multi-potent progenitor cells. We compared PVAT-derived cells to human bone marrow MSC for differentiation into adipogenic, osteogenic, and chondrogenic lineages. Following 14 days of differentiation, specific stains were utilized to detect lipid accumulation in adipocytes (Oil red O), calcific deposits in osteogenic cells (Alizarin Red), or glycosaminoglycans and collagen in chondrogenic cells (Masson's Trichrome). While bone marrow MSC efficiently differentiated into all three lineages, PVAT-derived cells had adipogenic and chondrogenic potential, but lacked robust osteogenic potential.

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Section: Representative Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells

Scott

Yang

Robich

et al. 2019

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“…However, PVAT’s response to metabolic derangements (e.g., obesity) appears to be heterogeneous. While abdominal aortic fat is mainly composed of white adipose tissue, thoracic aortic fat displays characteristics typical of brown adipose tissue, as shown by the high UCP‐1 expression (Boucher et al, ; Fitzgibbons et al, ). The above findings clearly underline the importance to shed further light on EAT and whole PVAT as markers of cardiometabolic risk and possible future therapeutic targets.…”

Section: Epicardial Adipose Tissue (Eat)mentioning

confidence: 99%

Impact of different ectopic fat depots on cardiovascular and metabolic diseases

Ferrara

Montecucco

Dallegri

2019

Journal Cellular Physiology

136

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A growing body of evidence is pointing out the pathophysiological role of fat accumulation in different organs. Ectopic fat depots within heart, liver, skeletal muscle, kidney, and pancreas as well as around blood vessels might be more associated to cardiometabolic risk than classical variables, such as body mass index.Among different mechanisms, lipid metabolism appears to be particularly influenced by ectopic fat depots. Indeed, intracellular accumulation of nonesterified fatty acids, and triglycerides promotes endoplasmic reticulum stress, mitochondrial uncoupling, oxidative stress, and altered membrane composition/function, finally promoting inflammatory response and cell death. The dysfunctional adipose tissue was shown to induce both local and systemic effects, with relevant clinical consequences. Epicardial fat and myocardial steatosis have been associated with the development of atrial fibrillation and ventricular dysfunction. Similarly perivascular adipose tissue appears to trigger atherosclerosis and hypertension. Nonalcoholic fatty liver disease has been recognized both as the hepatic manifestation of metabolic syndrome and as a cardiovascular (CV) risk factor. Importantly, the renal sinus fat emerged as a potential player in kidney dysfunction. Finally, both skeletal muscle and pancreatic fat depots have been indicated as potential endocrine modulators of insulin resistance.Considering the global rise in the prevalence of obesity, the understanding of mechanisms underlying ectopic fat accumulation represents an urgent need, with potential clinical implications for CV risk stratification. Here, we attempt to update the current knowledge of the different ectopic fat depots, focusing on underlying mechanisms and potential clinical implications.

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“…1e) [79,80]. Studies of human PVAT have shown that PVAT-derived adipocyte progenitor cell differentiation is dependent on Rab27a, a GTPase important for secretory vesicle trafficking [81]. One could imagine that the bi-directional communication between PVAT and the blood vessel relies on Rab27a-dependent trafficking and secretion of signaling molecules.…”

Section: Perivascular Adipose Tissue (Pvat)mentioning

confidence: 99%

In vitro tissue-engineered adipose constructs for modeling disease

2019

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Adipose tissue is a vital tissue in mammals that functions to insulate our bodies, regulate our internal thermostat, protect our organs, store energy (and burn energy, in the case of beige and brown fat), and provide endocrine signals to other organs in the body. Tissue engineering of adipose and other soft tissues may prove essential for people who have lost this tissue from trauma or disease. In this review, we discuss the applications of tissue-engineered adipose tissue specifically for disease modeling applications. We provide a basic background to adipose depots and describe three-dimensional (3D) in vitro adipose models for obesity, diabetes, and cancer research applications. The approaches to engineering 3D adipose models are diverse in terms of scaffold type (hydrogel-based, silk-based and scaffold-free), species of origin (H. sapiens and M. musculus) and cell types used, which allows researchers to choose a model that best fits their application, whether it is optimization of adipocyte differentiation or studying the interaction of adipocytes and other cell types like endothelial cells. In vitro 3D adipose tissue models support discoveries into the mechanisms of adipose-related diseases and thus support the development of novel anti-cancer or anti-obesity/diabetes therapies.

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Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation

Abstract: PVAT-APC from CABG donors express common adipocyte progenitor markers and differentiate into UCP1-containing adipocytes. Rab27a has an endogenous role in promoting the maturation of adipocytes from human PVAT-derived APC.

Cited by 13 publications

References 58 publications

Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells

Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells

Impact of different ectopic fat depots on cardiovascular and metabolic diseases

In vitro tissue-engineered adipose constructs for modeling disease

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