Periadventitial Adipose Tissue Research Articles

Vasorelaxation elicited by endogenous and exogenous hydrogen sulfide in mouse mesenteric arteries.

H2S causes vasorelaxation however there is considerable heterogeneity in the reported pharmacological mechanism of this effect. This study examines the contribution of endogenously released H2S in the regulation of vascular tone and the mechanism of H2S-induced vasorelaxation in small resistance-like arteries. Mesenteric arteries from C57 and eNOS-/- mice were mounted in myographs to record isometric force. Vasorelaxation responses to NaHS were examined in the presence of various inhibitors of vasorelaxation pathways. Expression and activity of the H2S-producing enzyme, cystathionine-γ-lyase (CSE), were also examined. CSE was expressed in vascular smooth muscle and perivascular adipose cells from mouse mesenteric artery. The substrate for CSE, L-cysteine, caused a modest vasorelaxation (35%) in arteries from C57 mice and poor vasorelaxation (10%) in arteries from eNOS-/- mice that was sensitive to the CSE inhibitor DL-propargylglycine. The fast H2S donor, NaHS, elicited a full and biphasic vasorelaxation response in mesenteric arteries (EC50 (1) 8.7 μM, EC50 (2) 0.6 mM), which was significantly inhibited in eNOS-/- vessels (P < 0.05), unaffected by endothelial removal, or blockers at any point in the NO via soluble guanylate cyclase and cGMP (NO-sGC-cGMP) vasorelaxation pathway. Vasorelaxation to NaHS was significantly inhibited by blocking K+ channels of the KCa and KV subtypes and the Cl-/HCO3- exchanger (P < 0.05). Further experiments showed that NaHS can significantly inhibit voltage-gated Ca2+ channel function (P < 0.05). The vasorelaxant effect of H2S in small resistance-like arteries is complex, involving eNOS, K+ channels, Cl-/HCO3- exchanger, and voltage-gated Ca2+ channels. CSE is present in the smooth muscle and periadventitial adipose tissue of these resistance-like vessels and can be activated to cause modest vasorelaxation under these in vitro conditions.

Empagliflozin ameliorates tunica adiposa expansion and vascular stiffening of the descending aorta in female db/db mice: an ultrastructure study

Background Obesity and aging are increasing globally and are known to be associated with adipose tissue and vascular stiffness, which are emerging as risk factors for the development of cardiometabolic and neurodegenerative diseases such as atherosclerosis, hypertension, type 2 diabetes mellitus (T2DM), metabolic syndrome, and Alzheimer’s disease. Therefore, we wished to test the hypothesis that the descending thoracic aorta may demonstrate aberrant ultrastructural remodeling that is ameliorated by empagliflozin, a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Methods Ten-week-old female wild-type control (C57BLKS/J) and db/db (BKS.Cg-Dock7m+/+Leprdb/J) mice were divided into three groups: lean untreated controls (CKC, n= 6), untreated db/db controls (DBC, n= 6) and DBC treated with empagliflozin (EMPA treated with 10 mg/kg/day for 10 weeks) (DBE, n= 6). Results This study focuses on ultrastructural remodeling of tunica adventitia and tunica adiposa (periadventitial adipose tissue) of the descending aorta in both DBC and DBE mice. In DBC mice (untreated db/db controls), major observational remodeling included differentiation from thermogenic brown adipose tissue to white adipose tissue with hypertrophy of white adipocytes; ruptured plasma membranes and liberation of toxic lipids into the matrix, which incited inflammation with mast cells and macrophages. These changes were ameliorated in DBE mice (DBC treated with empagliflozin). Conclusion Aberrant ultrastructural findings in DBC versus CKC and the amelioration with EMPA may provide better understanding how obesity and T2DM promote increased risk of vascular stiffness; a milieu for developing cardiovascular disease and target end-organ damage including nerve, retina, kidney and brain. Additionally, these findings may help us to better understand why obesity and T2DM result in the loss of homeostatic anticontractile function of tunica adiposa .

Morphological study on periadventitial adipose tissue of the aortic arch in a rabbit model of obesity: Preliminary results

Morphological study on periadventitial adipose tissue of the aortic arch in a rabbit model of obesity: Preliminary results

Periadventitial adipose tissue modulates the effect of PROLI/NO on neointimal hyperplasia

BackgroundPeriadventitial delivery of nitric oxide (NO) inhibits neointimal hyperplasia; however, the effect of periadventitial adipose tissue on the efficacy of NO at inhibiting neointimal hyperplasia has not been studied. The aim of our study was to assess the effect of NO in the presence and absence of periadventitial adipose tissue. We hypothesized that removal of periadventitial adipose tissue will increase neointimal formation and that NO will be more effective at inhibiting neointimal hyperplasia. MethodsThe effect of NO on 3T3 fibroblasts, adventitial fibroblast (AF), and vascular smooth muscle cell (VSMC) proliferation was assessed by 3H-thymidine incorporation in adipocyte-conditioned or regular media. The rat carotid artery balloon injury model was performed on male Sprague–Dawley rats. Before balloon injury, periadventitial adipose tissue was removed (excised model) or remained intact (intact model). Treatment groups included injury or injury with periadventitial application of PROLI/NO. Adiponectin receptor (AR) levels were assessed via immunofluorescence. ResultsAdipocyte-conditioned media had an antiproliferative effect on 3T3 and AF and a proproliferative effect on VSMC in vitro. Interestingly, NO was less effective at inhibiting 3T3 and AF proliferation and more effective at inhibiting VSMC proliferation in adipocyte-conditioned media. In vivo, the excised group showed increased neointimal hyperplasia 2 wk after surgery compared with the intact group. NO reduced neointimal hyperplasia to a greater extent in the excised group compared with the intact group. Although NO inhibited or had no impact on AR levels in the intact group, NO increased AR levels in media and adventitia of the excised group. ConclusionsThese data show that periadventitial adipose tissue plays a role in regulating the arterial injury response and the efficacy of NO treatment in the vasculature.

Сосудистая дисфункция и периадвентициальная жировая ткань

Сосудистая дисфункция и периадвентициальная жировая ткань

High-speed intravascular spectroscopic photoacoustic imaging at 1000 A-lines per second with a 0.9-mm diameter catheter.

Intravascular spectroscopic photoacoustic technology can image atherosclerotic plaque composition with high sensitivity and specificity, which is critical for identifying vulnerable plaques. Here, we designed and engineered a catheter of 0.9 mm in diameter for intravascular photoacoustic (IVPA) imaging, smaller than the critical size of 1 mm required for clinical translation. Further, a quasifocusing photoacoustic excitation scheme was developed for the catheter, producing well-detectable IVPA signals from stents and lipids with a laser energy as low as ~30 μJ/pulse. As a result, this design enabled the use of a low-energy, high-repetition rate, ns-pulsed optical parametric oscillator laser for high-speed spectroscopic IVPA imaging at both the 1.2-μm and 1.7-μm spectral bands for lipid detection. Specifically, for each wavelength, a 1-kHz IVPA A-line rate was achieved, ~100-fold faster than previously reported IVPA systems offering a similar wavelength tuning range. Using the system, spectroscopic IVPA imaging of peri-adventitial adipose tissue from a porcine aorta segment was demonstrated. The significantly improved imaging speed, together with the reduced catheter size and multiwavelength spectroscopic imaging ability, suggests that the developed high-speed IVPA technology is of great potential to be further translated for in vivo applications.

Chemerin and CMKLR1 expression in human arteries and periadventitial fat: a possible role for local chemerin in atherosclerosis?

BackgroundDepending on their anatomical location, different fat depots have a different capacity to produce bioactive peptides, called adipokines. Adipokines produced by periadventitial fat have been implicated in the pathogenesis of vascular disease, including atherosclerosis. Chemerin is an adipokine with an established role in immunity, adipose tissue function and metabolism, acting in autocrine, paracrine and endocrine manners. We investigated the protein expression of chemerin and its receptor, CMKLR1, in human aortas, coronary vessels and the respective periadventitial adipose tissue and correlated their expression with the presence of atherosclerosis.MethodsImmunohistochemistry for chemerin and CMKLR1 was performed on human aortic and coronary artery samples including the periadventitial adipose tissue. Aortic and coronary atherosclerotic lesions were assessed using the AHA classification.ResultsChemerin immunopositivity was noticed in both periadventitial fat depots, in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Periadventitial fat and foam cell chemerin immunopositivity was statistically significantly correlated with the severity of atherosclerosis in both locations. CMKLR1 was expressed in vascular smooth muscle cells and foam cells in aortic and coronary vessels with atherosclerotic lesions. CMKLR1 immunostaining in foam cells was statistically significantly correlated with aortic atherosclerosis.ConclusionsOur results lend some support to a presumable role of locally produced chemerin in the progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor. Further research will elucidate the role of chemerin signaling in atherosclerosis.

Triactome: neuro-immune-adipose interactions. Implication in vascular biology.

Understanding how the precise interactions of nerves, immune cells, and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue (PAAT), we recently designated tunica adiposa (in brief, adiposa like intima, media, and adventitia). Today, atherosclerosis is considered an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy, and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. PAAT expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic) signaling proteins collectively dubbed adipokines. However, the role of vascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro–immune–adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

Adiponectin/T-cadherin and apelin/APJ expression in human arteries and periadventitial fat: implication of local adipokine signaling in atherosclerosis?

Adipose tissue is considered an endocrine organ, producing bioactive peptides, called adipokines. Adipokines produced by periadventitial fat have been implicated in the pathogenesis of vascular disease, including atherosclerosis. Adiponectin has established antiatherogenic actions, while the role of T-cadherin as an adiponectin receptor is not fully elucidated. The apelinergic system, consisting of apelin and its APJ receptor, is a mediator of various cardiovascular functions and may also be involved in the atherosclerotic process. We investigated the protein expression of adiponectin, T-cadherin, apelin and APJ in human aortas, coronary vessels, and the respective periadventitial adipose tissue and correlated their expression with the presence of atherosclerosis and clinical parameters. Immunohistochemistry for adiponectin, T-cadherin, apelin, and APJ was performed on human aortic and coronary artery samples including the periadventitial adipose tissue. Aortic and coronary atherosclerotic lesions were assessed using the american heart association (AHA) classification. Adiponectin immunostaining, of varied intensity, was detected only in adipocytes, while T-cadherin was localized to vascular smooth muscle cells (VSMCs) and endothelial cells. Apelin immunostaining was detected in adipocytes, VSMCs, endothelial cells, and foam cells in atherosclerotic lesions, while APJ was found in VSMCs and endothelia. Periadventitial adiponectin and VSMC T-cadherin expression were negatively correlated with atherosclerosis in both sites, as was VSMC apelin expression. Several other - depot specific - associations were observed. Our results suggest a possible role for T-cadherin as a mediator of antiatherogenic adiponectin actions, while they support the putative antiatherogenic profile for apelin and its APJ receptor in human arteries. Further research is absolutely necessary to confirm these notions. Periadventitial adipose tissue adipokines are implicated in vascular physiology and pathology. Adiponectin/T-cadherin and apelin/APJ immunoreactivity is detected in human aortas and coronary arteries. Adiponectin/T-cadherin and apelin/APJ expression patterns were found to be inversely associated with human aortic and coronary atherosclerosis.

Abstract 467: Nitric Oxide-Mediated Regulation of the Adiponectin-Adiponectin Receptor Pathway Following Arterial Injury

Objectives Nitric oxide (NO) has been shown to limit the development of neointimal hyperplasia; however, little is known about its effects on the adventitia. Adiponectin is a molecule that originates from periadventitial adipose tissue and has been shown to negatively regulate neointimal growth. Thus, we hypothesize that removal of periadventitial fat from the arterial wall will negatively impact the ability of NO to inhibit the development of neointimal hyperplasia following injury. Methods The carotid artery injury model was performed on 11-week-old Sprague Dawley rats. Animal models underwent either removal of all periadventitial fat from the artery at the time of surgery (absent) or no disturbance of the periadventitial fat (present). Treatment groups included control, injury, and injury + NO (PROLI/NO, 10mg). Arteries were harvested at 2 weeks. Morphometric analysis was performed using ImageJ software. Immunofluorescent staining was performed for the adiponectin receptor (AR) and assessed using blinded grading (scale 0-4). Results Morphometric analysis revealed a 29% increase in neointima development in the absent vs. present group (p&lt;0.001). With the application of NO, there was a greater decrease in intima area in the absent than the present group (93% vs. 77%, p&lt;0.001). The results were similar for media area (50% vs. 37%, p&lt;0.001) and the intima/media area ratio (86% vs. 65%, p&lt;0.001). While AR staining showed no significant difference in the media or adventitia with the application of NO in the present group, AR staining was significantly increased in both the media (57%, p=0.009) and adventitia (37%, p&lt;0.05) with the application of NO in the absent group. Conclusions Removal of the source of periadventitial adiponectin resulted in more neointimal hyperplasia following arterial injury, but a paradoxical NO-mediated increase in AR levels and corresponding responsiveness to NO therapy. These data suggest that AR expression is upregulated in the absence of adiponectin by NO. Further studies that identify the mechanism by which NO may regulate adiponectin may provide a novel therapeutic target to prevent neointimal hyperplasia.

Leptin-dependent and leptin-independent paracrine effects of perivascular adipose tissue on neointima formation.

Clinical and experimental evidence suggests that periadventitial adipose tissue may modulate vascular lesion formation. The aim of this study was to determine the role of perivascular leptin expression on neointima formation and to differentiate it from local inflammation and systemically elevated leptin levels. Increased neointima formation after carotid artery injury was observed in hyperleptinemic, diet-induced obese wild-type mice, but not in leptin-deficient ob/ob mice. High-fat diet was associated with increased leptin expression in visceral adipose tissue (VAT) as well as in perivascular adipose tissue. Perivascular leptin overexpression achieved by adenoviral vectors enhanced intimal cell proliferation and neointima formation in wild-type mice, but not in leptin receptor-deficient mice. Perivascular transplantation of VAT from high-fat diet-induced obese wild-type mice around the carotid artery of immunodeficient mice also promoted neointima formation, without affecting body weight or systemic leptin levels, and this effect was absent, if VAT from ob/ob mice was used. On the contrary, perivascular transplantation of VAT from ob/ob mice fed high-fat diet, characterized by marked immune cell accumulation, promoted neointimal hyperplasia also in the absence of leptin. In vitro, recombinant leptin and VAT-conditioned medium increased human arterial smooth muscle cell proliferation in a (partly) leptin-dependent manner. Our findings suggest that locally elevated leptin levels may promote neointima formation, independent of obesity and systemic hyperleptinemia, but also underline the importance of perivascular inflammation in mediating the increased cardiovascular risk in obesity.

Adipoparacrinology of Atherosclerosis: Evidence Updated

Abstract: Recently, the secretory - endocrine, paracrine and autocrine - phenotype of adipose tissue, consisting of adipo-cytes, stromovascular cells and immune cells, has increasingly been recognized. In humans, adipose tissue is partitioned into two large depots (subcutaneous and visceral) and many small depots associated with heart, blood vessels, major lymph nodes, pancreas, prostate gland, ovaries. Accordingly, two major subfields of adipobiology have emerged, adi-poendocrinology (studying the endocrine activity of adipose tissue) and adipoparacrinology (studying the paracrine activ-ity of adipose tissue). Traditional concept of the pathogenesis of atherosclerosis focuses on intimal surface, where endo-thelial dysfunction expressed by an “inside-out” inflammatory process triggers the formation of atherosclerotic plaque. The present short review highlights evidence for the possible role of dysfunctional paracrine activity of epicardial adipose tissue and of periadventitial adipose tissue in an “outside-in” pathway in the development of coronary and peripheral athe-rosclerosis, respectively. Such a paradigm may have various therapeutic applications including in coronary artery bypass surgery.

Adipoparacrinology – vascular periadventitial adipose tissue (tunica adiposa) as an example

Human adipose tissue is partitioned into two large depots (subcutaneous and visceral), and many small depots associated with internal organs, e.g. heart, blood vessels, major lymph nodes, pancreas, prostate gland and ovaries. Since the adipose 'Big Bang' led to the discovery of leptin (Zhang, Proenca, Maffei, Barone, Leopold and Friedman, Nature 1994;372:425-32), adipose tissue has been seen not merely as a lipid store, but as a secretory - endocrine and paracrine - organ, particularly in the pathogenesis of a number of diseases. Accordingly, two major sub-fields of adipobiology have emerged, viz. adipoendocrinology and adipoparacrinology, the latter herein being illustrated by PAAT (periadventitial adipose tissue) in vascular walls. A long-standing paradigm holds that the vascular wall consists of three coats, tunica intima, tunica media and tunica adventitia. It is now imperative that 'to further elucidate vascular function, we should no longer, as hitherto, separate adventitia and PAAT from the vascular wall, but keep them attached and in place, and subject to thorough examination' (Chaldakov, Fiore, Ghenev, Stankulov and Aloe, Int Med J 2000;7:43-9; Chaldakov, Stankulov and Aloe, Atherosclerosis 2001;154:237-8; Chaldakov GN, Stankulov IS, Fiore M, Ghenev PI and Aloe L, Atherosclerosis 2001;159:57-66). From the available data, we propose that it is time to rethink about vascular wall composition, and suggest that the PAAT may be considered the fourth and outermost vascular coat, hence, tunica adiposa (regarding the proximal segment of coronary artery, it is the innermost part of the EAT (epicardial adipose tissue) situated around the coronary adventitia). Its significance in the pathogenesis and therapy of CMDs (cardiometabolic diseases), particularly atherosclerosis and hypertension, requires further basic, translational and clinical studies.

Vasodilator signals from perivascular adipose tissue

Visceral fat has been linked to metabolic disturbances and increased risk for cardiovascular disease and type 2 diabetes. Recent studies propose a paracrine role for periadventitial adipose tissue in the control of arterial vascular tone. This regulation depends on the anatomical integrity of the vessels and involves a transferable mediator(s) (adipokine) released from either periadventitial adipocytes or perivascular adipose tissue. Although a number of adipokines with vasoactive properties have been identified, a still unidentified adipocyte-derived relaxing factor (ADRF) plays a major role in the periadventitial vasoregulation of visceral arteries, such as the aorta and mesenteric arteries. ADRF is released by visceral periadventitial adipocytes and primarily produces endothelium-independent vasorelaxation by opening voltage-dependent (K(v) ) K(+) channels in the plasma membrane of smooth muscle cells. At least in part, KCNQ (K(v) 7) channels could represent the subtype of K(v) channels involved. Glibenclamide-sensitive K(ATP) channels are not involved or play a minor role. The 'third gas', namely H(2) S, could represent ADRF. Alterations in the paracrine control of arterial tone by visceral periadventitial adipose tissue have been found in animal models of hypertension and metabolic disease. ADRF, or perhaps its putative targets, might represent exciting new targets for the development of drugs for treatment of cardiovascular and metabolic disorders. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.

Механізми впливу сірководню на скоротливу активність гладеньких м’язів судин щурів

The effect of endogenous and exogenous hydrogen sulfide (H2S) on contractile activity of vascular smooth muscle (VSM) was studied. The introduction of substrate synthesis H2S L-cysteine and its donor NaHS in vitro caused concentration-dependent relaxation of VSM of aorta and portal vein. Low concentrations of hydrogen sulfide donor (10(-5) mol/L) caused vasoconstriction of both types of the vessels. It was shown that the reaction of relaxation of VSM in response to NaHS is independent from endothelium. It was revealed that VSM of portal vein are more sensitive to the effects of H2S than VSM of aorta. Removing of aorta periadventitial adipose tissue showed no relaxation reply to the hydrogen sulfide donor NaHS in 70% of experiments. Some of the cellular mechanisms of hydrogen sulfide action were established, namely relaxation of aorta is depended on K(ATP) channel activation. This is manifested by a lack of relaxation of the aortic VSM due to K(ATP) channel inhibitor glibenclamide.

The Vascular Adventitia: Its Role in the Arterial Injury Response

The belief that the adventitia serves only a structural purpose has changed over the last decade. Studies have begun to elucidate the role the adventitia plays in the arterial response to injury. The adventitial fibroblast plays an integral part in the development of neointimal hyperplasia. Adiponectin, an adipokine produced from periadventitial adipose tissue, exhibits numerous vasoprotective properties. Stem cells arise, in part, from the adventitia, and stem cell recruitment into the adventitia from the vasa vasorum has been shown to be important in the development of neointimal hyperplasia. The exact role the vasa vasorum plays in neointimal growth is poorly understood and different studies endorse conflicting viewpoints. Thus, understanding the nuances of adventitial pathophysiology will allow us to better appreciate the mechanisms behind the pathology of neointimal hyperplasia. This review will summarize recent findings on the active role the adventitia plays toward the development of neointimal hyperplasia.

Hydrogen sulfide: synthesis and function in the adipose tissue

Apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H 2 S) is the third gaseous mediator in mammals. H 2 S is synthesized from L-cysteine by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), or by sequential action of alanine aminotransferase and 3-mercaptopyruvate sulfurtransferase. In the cardiovascular system, H 2 S is involved in the regulation of vascular tone and blood pressure, inhibits atherogenesis, and protects myocardium from ischemia-reperfusion injury. Recent studies indicate that H 2 S is synthesized also in the adipose tissue. Hydrogen sulfide produced in periadventitial adipose tissue (tunica adiposa) of the blood vessels induces vasodilation by activating K + channels in smooth muscle cells. On the other hand, H 2 S inhibits basal and insulin-stimulated glucose uptake in visceral adipose tissue, and may be involved in the pathogenesis of insulin resistance. H 2 S production in periadventitial adipose tissue is stimulated by vasoconstrictors and aortic banding-induced hypertension and downregulated by aging. H 2 S signaling in adipose tissue may be affected by pharmacotherapy. Lipid-soluble statins (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors) increase H 2 S level in periadventitial adipose tissue and thus augment its anticontractile effect on the blood vessels. This effect of statins results from the depletion of ubiquinone - a component of mitochondrial respiratory chain - and the impairment of mitochondrial H 2 S oxidation. Adipobiology 2010; 2: 41-50.

Adipokines in Periaortic and Epicardial Adipose Tissue: Differential Expression and Relation to Atherosclerosis

Adipokines are protein products of adipose tissue with paracrine and endocrine actions, which have been implicated in the pathogenesis of cardiovascular disease. Locally produced adipokines, especially by periadventitial adipose tissue, may affect vascular physiology and pathology. We investigated the expression of adiponectin, visfatin, leptin and novel adipokines chemerin and vaspin in human periaortic and epicardial adipose tissue, as well as their correlation to aortic and coronary atherosclerosis. Standard immunohistochemical staining for the adipokines was performed on samples of human periaortic, pericoronary and apical epicardial adipose tissue. Atherosclerotic lesions of the adjacent vascular wall were assessed using the AHA classification. Adipokines were expressed in periadventitial and apical epicardial adipose tissue and - except for adiponectin - in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Aortic atherosclerosis was positively correlated with chemerin, vaspin, visfatin and leptin periaortic fat expression. Coronary atherosclerosis was positively correlated with chemerin and visfatin pericoronary fat expression. Adipose tissue adiponectin expression was negatively correlated to atherosclerosis in both locations. Expression of adipokines in apical epicardial fat was not associated with atherosclerosis. Our results show: a) a different expression pattern of adiponectin, visfatin, leptin, chemerin and vaspin in periaortic, pericoronary and apical epicardial adipose tissue, b) a correlation of these adipokines with either aortic or coronary atherosclerosis or both in a pattern characteristic for each adipokine and suggest that locally produced adipokines might differently affect the atherosclerotic process in different locations.

Periadventitial Adipose Tissue Promotes Endothelial Dysfunction via Oxidative Stress in Diet-Induced Obese C57Bl/6 Mice

Biological substances derived from perivascular fat modulate vascular tone, thus alterations in periadventitial adipose tissue (PVAT) may aggravate endothelial dysfunction in obesity. Male C57Bl/6 mice were fed either a high-fat diet or standard laboratory chow for 8 months. Vascular responses were studied in organ bath chambers from abdominal aortic ring preparations in the absence or presence of PVAT. The amount of PVAT as well as the cross-sectional area of adipocytes were increased in obese mice. In the presence of PVAT, obese aortas displayed impaired endothelium-dependent vasodilation whereas endothelium-independent vasodilatation was unaltered. Endothelium-dependent vasodilatation was restored after removal of PVAT and after reducing superoxide and hydrogen peroxide formation in the vascular wall by Tiron or polyethylene-glycol-catalase, respectively. PVAT from obese mice showed increased formation of hydrogen peroxide and superoxide. The PVAT-derived oxidative stress was abolished by pretreatment with the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase inhibitor, apocynin. The anti-contractile function of PVAT found in lean mice was completely abolished in obese mice, but partially restored after pretreatment with Tiron. The mRNA expressions of monocyte chemotactic protein-1, leptin and NADPH oxidase were markedly higher in the PVAT of obese than lean mice. PVAT promotes endothelial dysfunction in diet-induced obese C57Bl/6 mice via mechanisms that are linked to increased NADPH oxidase-derived oxidative stress and increased production of pro-inflammatory cytokines.

State-of-the-artery: periadventitial adipose tissue (tunica adiposa)

Traditional view considers that the arterial wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerosis develops, are consistently surrounded by periadventitial adipose tissue (PAAT). Here we update growing information about PAAT, and conceptualize it as the fourth coat of arterial wall, that is, tunica adiposa (in brief, adiposa, like intima, media, adventitia). Recent evidence has revealed that adipose tissue expresses not only metabolic, but also secretory (endo- and paracrine) phenotype, producing/releasing a large number of signaling proteins collectively termed adipokines. Through paracrine ("vasocrine") way, adiposa-derived mediators may contribute to various arterial functions such as contraction-relaxation, smooth muscle cell growth, inflammation, hemostasis, and innervation, hence to "outside-in" signaling pathway of atherogenesis. Biomedical Reviews 2009; 20: 41-44.