Perivascular Adipose Tissue Inhibits Endothelial Function of Rat Aortas via Caveolin-1

Lee, Michelle Hui Hsin; Chen, Shiu Jen; Tsao, Cheng Ming; Wu, Chang‐Chieh

doi:10.1371/journal.pone.0099947

Cited by 40 publications

(34 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have suggested a contributory role of PVAT to endothelial dysfunction. Lee et al reported that in obesity, PVAT reduces NO production through increased expression of caveolin-1, which negatively regulates endothelial NO synthase (eNOS) [24]. PVAT also may induce endothelial dysfunction via protein kinase C-β dependent phosphorylation and inactivation of eNOS [25].…”

Section: Discussionmentioning

confidence: 99%

Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis

Horimatsu

Patel

Prasad

et al. 2018

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

Purpose Perivascular adipose tissue (PVAT) surrounds the arterial adventitia and plays an important role in vascular homeostasis. PVAT expands in obesity, and inflamed PVAT can locally promote endothelial dysfunction and atherosclerosis. Here, using adipose tissue transplantation, we tested the hypothesis that expansion of PVAT can also remotely exacerbate vascular disease. Methods Fifty milligrams of abdominal aortic PVAT was isolated from high-fat diet (HFD)-fed wild-type mice and transplanted onto the abdominal aorta of lean LDL receptor knockout mice. Subcutaneous and visceral adipose tissues were used as controls. After HFD feeding for 10 weeks, body weight, glucose/insulin sensitivity, and lipid levels were measured. Adipocytokine gene expression was assessed in the transplanted adipose tissues, and the thoracic aorta was harvested to quantify atherosclerotic lesions by Oil-Red O staining and to assess vasorelaxation by wire myography. Results PVAT transplantation did not influence body weight, fat composition, lipid levels, or glucose/insulin sensitivity. However, as compared with controls, transplantation of PVAT onto the abdominal aorta increased thoracic aortic atherosclerosis. Furthermore, PVAT transplantation onto the abdominal aorta inhibited endothelium-dependent relaxation in the thoracic aorta. MCP-1 and TNF-α expression was elevated, while adiponectin expression was reduced, in the transplanted PVAT tissue, suggesting augmented inflammation as a potential mechanism for the remote vascular effects of transplanted PVAT. Conclusions These data suggest that PVAT expansion and inflammation in obesity can remotely induce endothelial dysfunction and augment atherosclerosis. Identifying the underlying mechanisms may lead to novel approaches for risk assessment and treatment of obesity-related vascular disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis

Horimatsu

Patel

Prasad

et al. 2018

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

show abstract

“…Aortic NO production was diminished, whereas Cav-1 protein expression was significantly increased in aortas after PVAT treatment. The depletion of caveolae by methyl-β-cyclodextrin abolished the effects of PVAT on the enhancement of vasoconstriction and reversed the impairment of aortic NO production [49]. Interestingly, chemerin is a peptide that is abundantly expressed in PVAT and contracts isolated rat thoracic aortas, superior mesenteric arteries, and mesenteric resistance arteries.…”

Section: Pvat Constricts Vesselsmentioning

confidence: 99%

The role of perivascular adipose tissue in vasoconstriction, arterial stiffness, and aneurysm

Villacorta

Chang

2015

Hormone Molecular Biology and Clinical Investigation

View full text Add to dashboard Cite

Since the “rediscovery” of brown adipose tissue in adult humans, significant scientific efforts are being pursued to identify the molecular mechanisms to promote a phenotypic change of white adipocytes into brown-like cells, a process called “browning”. It is well documented that white adipose tissue (WAT) mass and factors released from WAT influence the vascular function and positively correlate with cardiac arrest, stroke, and other cardiovascular complications. Similar to other fat depots, perivascular adipose tissue (PVAT) is an active endocrine organ and anatomically surrounds vessels. Both brown-like and white-like PVAT secrete various adipokines, cytokines, and growth factors that either prevent or promote the development of cardiovascular diseases (CVDs) depending on the relative abundance of each type and their bioactivity in the neighboring vasculature. Notably, pathophysiological conditions, such as obesity, hypertension, or diabetes, induce the imbalance of PVAT-derived vasoactive products that promote the infiltration of inflammatory cells. This then triggers derangements in vascular smooth muscle cells and endothelial cell dysfunction, resulting in the development of vascular diseases. In this review, we discuss the recent advances on the contribution of PVAT in CVDs. Specifically, we summarize the current proposed roles of PVAT in relationship with vascular contractility, endothelial dysfunction, neointimal formation, arterial stiffness, and aneurysm.

show abstract

“…It is crucial for Ca 2+ entry through Ca 2+ channels [19,45]. The endothelial function of rat aortas is inhibited by perivascular adipose tissue via Cav-1 [46]. Disruption of caveolae inhibited TRPC6 activity in bovine aortic endothelial cells [47].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension

Mu¹,

Lin²,

Yan³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Alterations in intracellular Ca²⁺ concentration ([Ca²⁺]_i) underlie the pathogenesis of various cardiovascular diseases. Caveolin-1 (Cav-1) is the primary functional protein associated with caveolae, which are invaginations in the plasma membrane, and is a regulator of [Ca²⁺]_i signaling. Caveolae and Cav-1 increase the activity of store-operated Ca²⁺ channels (SOCC) in rat pulmonary arterial smooth muscle cells (PASMCs), and these enhancing effects were more pronounced in rats with pulmonary hypertension (PH). Classical transient receptor potential (TRPC) proteins are highly expressed in vascular smooth muscle cells, and these proteins form functional receptor-operated Ca²⁺ channels (ROCC) and SOCC in PASMCs. Previous studies suggested that functional and structural changes in aortas might occur during the pathological process of PH. Our data demonstrated that Cav-1 and TRPC were also abundant in the aorta smooth muscle cells (AoSMCs) of PH rats. However, previous PH research primarily focused on Ca²⁺ channels in pulmonary arteries, but not functional changes in Ca²⁺ channels in aortas. The contribution of Cav-1 of AoSMCs to alterations of Ca²⁺ signaling in aortic functions during the pathological process of PH has not been fully characterized. Therefore, this study investigated alterations in Cav-1 expression and the relationship of these changes to Ca²⁺ channels in AoSMCs of PH rats. Methods: The present study examined physiological caveolae and Cav-1 expression and characterized the function of altered Cav-1 expression in rat aortas with PH. Results: The appearance of caveolae with Cav-1 expression increased significantly in the aortas of rats with PH, but TRPC1 and TRPC6 expression was not altered. In vitro experiments demonstrated that caveolae contributed to phenylephrine, endothelin-1, and 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced aortic vasoreactivity, but KCl and cyclopiazonic acid had no effect, which suggests the vital ability of Cav-1 to regulate ROCC activity. The introduction of Cav-1 scaffolding domain peptide enhanced OAG-induced ROCC function in primary AoSMCs. Conclusion: Cav-1 is specifically associated with ROCC in aortas and plays a vital role in altering vasoreactivity, which affects cardiovascular diseases pathology. Caveolae and Cav-1 up-regulation may affect the function of ROCC in rat models of PH.

show abstract

Perivascular Adipose Tissue Inhibits Endothelial Function of Rat Aortas via Caveolin-1

Cited by 40 publications

References 42 publications

Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis

Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial Function and Atherosclerosis

The role of perivascular adipose tissue in vasoconstriction, arterial stiffness, and aneurysm

Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension

Contact Info

Product

Resources

About