Influence Of Perivascular Adipose Tissue Research Articles

Influence of Perivascular Adipose Tissue on Microcirculation: A Link Between Hypertension and Obesity.

Alterations in microcirculation play a crucial role in the pathogenesis of cardiovascular and metabolic disorders such as obesity and hypertension. The small resistance arteries of these patients show a typical remodeling, as indicated by an increase of media or total wall thickness to lumen diameter ratio that impairs organ flow reserve. The majority of blood vessels are surrounded by a fat depot which is termed perivascular adipose tissue (PVAT). In recent years, data from several studies have indicated that PVAT is an endocrine organ that can produce a variety of adipokines and cytokines, which may participate in the regulation of vascular tone, and the secretory profile varies with adipocyte phenotype and disease status. The PVAT of lean humans largely secretes the vasodilator adiponectin, which will act in a paracrine fashion to reduce peripheral resistance and improve nutrient uptake into tissues, thereby protecting against the development of hypertension and diabetes. In obesity, PVAT becomes enlarged and inflamed, and the bioavailability of adiponectin is reduced. The inevitable consequence is a rise in peripheral resistance with higher blood pressure. The interrelationship between obesity and hypertension could be explained, at least in part, by a cross-talk between microcirculation and PVAT. In this article, we propose an integrated pathophysiological approach of this relationship, in order to better clarify its role in obesity and hypertension, as the basis for effective and specific prevention and treatment.

Imbalance of helper T cell subtypes and adipokine secretion in perivascular adipose tissue as a trigger of atherosclerosis in chronic Porphyromonas gingivalis W83 infection

Periodontal disease, a prevalent oral disease, is an independent risk factor for atherosclerosis. Porphyromonas gingivalis (P.g), a keystone pathogen of periodontal disease, contributes to the pathogenesis of atherosclerosis. However, the exact mechanism remains unclear. An increasing number of studies have proposed the atherogenic influence of perivascular adipose tissue (PVAT) in pathological conditions including hyperlipidemia and diabetes. Nevertheless, the role of PVAT in atherosclerosis promoted by P.g infection has not been explored. In our study, we investigated the association between P.g colonization in PVAT and progression of atherosclerosis through experiments on clinical samples. We further investigated P.g invasion of PVAT, PVAT inflammation, aortic endothelial inflammation, aortic lipid deposition, and systemic inflammation in C57BL/6 J mice with or without P.g infection at 20, 24, and 28 weeks of age. PVAT inflammation, characterized by imbalance in Th1/Treg and dysregulated adipokine levels, was associated with P.g invasion, preceding endothelial inflammation that occurred independently of its direct invasion. The phenotype of systemic inflammation coincided with that of PVAT inflammation, but systemic inflammation occurred after endothelial inflammation. Therefore PVAT inflammation in early atherosclerosis could be a primary trigger of aortic endothelial inflammation and lipid deposition in chronic P.g infection, through the dysregulated paracrine secretion of T helper-1-related adipokines.

The Influence of Perivascular Adipose Tissue on Vascular Function in a Rabbit Model

The recent acknowledgment of the paracrine role of perivascular adipose tissue (PVAT) in vascular modulation has been supported by many studies investigating major arteries in several animal models and humans. The influence of PVAT on the functional activity of the vascular bed has been a matter of debate, whether it is an anticontractile effect with protective roles or a pro-contractile effect, investigations are underway to address this obscurity. In this investigation, we have studied the effects of vasoconstrictors, phenylephrine and noradrenaline, and vasorelaxants, carbachol and s-nitroso-n- acetylpenicillamine (SNAP), on subclavian and iliac rings with and without PVAT attached; and concentration-response curves were constructed accordingly. Levels of nitric oxide (NO) generated due to activation of the enzyme adenosine monophosphate-activated protein kinase (AMPK) by 5-Aminoimi- dazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) were measured in sub- clavian and iliac PVAT conditioned media. Additionally, Haematoxylin and Eosin staining was performed to analyze and compare the histological characteristics of both arteries. Subclavian and iliac rings with PVAT attached showed stronger contraction to phenylephrine and noradrenaline than that of rings without PVAT attached. At the same time, relaxation tests reported lower relaxation percentages in subclavian and iliac rings with PVAT attached compared to rings without PVAT attached in response to carbachol and SNAP. PVAT treated with AICAR generated higher levels of NO compared to levels of untreated PVAT. Conclusions drawn were the pro-contractile effects demonstrated by the PVAT especially in high concentrations of drugs used. In addition, histology analysis revealed characteristics of white adipose tissue in both PVATs.

Influence of perivascular adipose tissue on vasodilation in the renal artery of metabolic syndrome rats

Influence of perivascular adipose tissue on vasodilation in the renal artery of metabolic syndrome rats

Time-Dependent Differences in the Influence of Perivascular Adipose Tissue on Vasomotor Functions in Metabolic Syndrome

Metabolic syndrome (MetS) facilitates the development of cardiovascular disease due to atherosclerosis, which is accelerated by defects of the vascular endothelium. Vascular dysfunction in response to nitric oxide (NO) occurs in the mesenteric arteries of an animal model of MetS, SHRSP.Z-Leprfa/IzmDmcr (SHRSP.ZF) rats. Vascular responses to vasodilators are affected by perivascular adipose tissue (PVAT) that surrounds the outsides of arteries. In this study, we assessed the role of PVAT in vascular dysfunction observed in SHRSP.ZF. To determine the effects of PVAT on vasodilators in SHRSP.ZF and control Wistar-Kyoto (WKY) rats, we used organ bath bioassay techniques to assay acetylcholine and nitroprusside-induced relaxations of isolated mesenteric arterial ring preparations with PVAT intact or removed. A PVAT-mediated enhancement of relaxations induced by acetylcholine and nitroprusside occurred in SHRSP.ZF at 20 weeks of age, but not at 10 and 30 weeks, and did not occur in WKY. Furthermore, the enhancing effects of PVAT from SHRSP.ZF at 20 weeks could not be substituted by replacement with PVAT from either WKY or 30-week-old SHRSP.ZF, was inhibited by NO synthase inhibitor, and abolished by removal of the arteries' endothelium. Cyclic guanosine monophosphate (cGMP) accumulation elicited by nitroprusside was higher in SHRSP.ZF arteries with PVAT than arteries without PVAT at 20 weeks, but the enhancement of cGMP accumulation did not occur at 30 weeks. PVAT may regulate arterial tone by releasing diffusible vasorelaxing factor(s), which, through endothelium-derived NO production, compensates for impaired vasodilations at early stages of MetS.

212 Effects of perivascular adipose tissue and high fat feeding on vascular reactivity in the apoe–/–mouse

Perivascular adipose tissue (PVAT) surrounds the majority of blood vessels and has recently been suggested to play a role in the pathogenesis of atherosclerosis. PVAT exerts anti-contractile effects that are abolished in disease states, these effects could potentially modulate atherosclerosis. The aims of this study were to determine the influence of PVAT, age, high fat diet (HFD) and associated progression of atherosclerosis on isolated arterial reactivity. Male ApoE -/- mice were fed a high fat or standard chow diet for 8, 16 or 26 weeks. Aortic atherosclerotic lesion areas were analysed by en face quantification with Oil Red O. Contractile responses of thoracic aortae to cumulative doses of phenylephrine (1 × 10 –10 – 3 × 10 –5 M) or a maximal dose of serotonin (1 × 10 –5 M) were measured in PVAT intact or denuded vessels using myography. Endothelial function was evaluated by relaxation to acetylcholine (1 × 10 –5 M) on vessels pre-constricted with phenylephrine (1 × 10 –5 M). High fat feeding significantly increased the percentage of aortic area covered by atherosclerotic lesions in the ApoE -/- mouse at each time-point (standard chow versus HFD; 8 weeks: 0.11%±0.08 vs. 1.53% ± 0.21; 16 weeks: 1.28%±0.08 vs. 8.89%±0.80; 26 weeks: 2.79%±0.85 vs. 25.43%±2.65). PVAT significantly increased vasoconstrictor responses to phenylephrine at the 8 and 16 week time-points in HFD fed and age-matched controls (8 week chow: PVAT versus no PVAT P = 0.006, n = 12. 8 week HFD: PVAT versus no PVAT, P = 0.03, n = 10, 16 week chow: PVAT versus no PVAT P = 0.0001, n = 11. 16 week HFD: PVAT versus no PVAT, P = 0.004, n = 9). PVAT exerted anti-contractile effects in the 26 week controls (PVAT versus no PVAT P = 0.02, n = 7). PVAT exerted no effect on vessel contractility in the 26 week HFD group (HFD: PVAT versus no PVAT P=NS, n = 9). Contractile responses to serotonin were unaffected by atherosclerotic progression or the presence of PVAT. Endothelial dysfunction was observed in the 26 week chow cohort however, this was not demonstrated in the HFD groups. PVAT exerted no effect on aortic relaxation. In summary, PVAT modulated the vasoconstrictor responses of aortic segments to phenylephrine during atherosclerotic disease progression in the ApoE –/– mouse. However, relaxation in response to acetylcholine, an endothelium-dependent vasodilator, was not significantly altered by the presence of PVAT. These findings may have important implications in the pathogenesis of atherosclerosis. This research was funded by the British Heart Foundation.

Effect of resveratrol and orchidectomy on the vasorelaxing influence of perivascular adipose tissue.

Perivascular adipose tissue (PVAT) releases several adipo(cyto)kines. Some are vasoactive substances that elicit a net beneficial anticontractile effect. Resveratrol and testosterone are known to modulate adipo(cyto)kine release from adipose tissue and could therefore influence the anticontractile effect of PVAT. In vitro tension measurements were performed using thoracic aorta segments with and without adipose tissue from sham-operated or orchidectomized male Swiss mice. Concentration-response curves to norepinephrine (NOR) were constructed in the presence and absence of resveratrol (10 μM, 15 min) or the relaxant effect of resveratrol (10-100 μM) was investigated after inducing tone with NOR (5 μM). Aortas with PVAT displayed significantly attenuated contractions to NOR compared with aortas without PVAT. In aortas without PVAT, resveratrol (10 μM) significantly decreased NOR responses and elicited concentration-dependent (10-100 µM) relaxations. However, in aortas with adherent PVAT, resveratrol (10 μM) neither decreased NOR responses, nor did resveratrol (10-100 µM) induce arterial relaxations. The anticontractile effect of PVAT was less pronounced in the presence of resveratrol and unaltered by orchidectomy. Orchidectomy did not influence contractions induced by NOR. Orchidectomy does not modulate the anticontractile capacity of PVAT, while resveratrol decreases the vasorelaxing influence of PVAT. The positive effects associated with resveratrol addition are neutralized by the presence of PVAT. This is thought to result from a dual effect of resveratrol: (1) inhibition of the influence of vasodilatory adipo(cyto)kines and (2) a direct relaxant effect on the vascular smooth muscle. Overall, the beneficial relaxing effect of resveratrol is lost in mice thoracic aorta surrounded by PVAT.

Perivascular Adipose Tissue and Cardiometabolic Disease

BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity.CONTENT: Perivascular adipose tissue (PVAT) is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines’. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis.SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease.KEYWORDS: obesity, perivascular adipose tissue, PVAT, cardiometabolic disease, adipokine

The influence of perivascular adipose tissue on vascular homeostasis

The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT.

Relationship between myocardial bridges and reduced coronary atherosclerosis in patients with angina pectoris

BackgroundA myocardial bridge (MB) is a band of myocardium covering a coronary artery segment, typically located in the left anterior descending coronary artery (LAD). Bridged segments of the coronary artery are isolated from the influence of perivascular adipose tissue. The aims of this study were to investigate the relationship between MBs and atherosclerosis in bridged LAD segments and to evaluate whether perivascular adipose tissue is involved in this relationship. MethodsMBs were identified in the coronary arteries of patients referred for diagnostic cardiac CT. The calcium score of MBs of the LAD or, in patients without LAD-MBs, of a corresponding LAD segment at the same distance from its origin and over the same length was measured. ResultsOf 128 patients, 56 (44%) had in total 73 MBs. The mean MB length was 22±14mm and the median MB thickness was 0.8mm (interquartile range 0.3–2.1mm). MBs in the LAD were present in 40 patients (31%). The calcium score was 0 in 95% of the LAD segments with MBs compared with 52% of the corresponding LAD segments without MBs. The association between LAD-MBs and calcium score (OR 0.06, 95% CI 0.01–0.25) was not influenced by age and gender, but was attenuated by local perivascular adipose tissue thickness (OR 0.35, 95% CI 0.04–2.70). ConclusionsCoronary artery segments covered with an MB have a lower calcium score than segments without an MB. The association between MBs and calcium scores was influenced by local perivascular adipose tissue thickness.

Perivascular adipose tissue and vascular disease

Perivascular adipose tissue is a local deposit of adipose tissue surrounding the vasculature. Perivascular adipose tissue is present throughout the body and has been shown to have a local effect on blood vessels. The influence of perivascular adipose tissue on the vasculature changes with increasing adiposity. This article describes the anatomy and pathophysiology of perivascular adipose tissue and the experimental evidence supporting its local adverse effect on the vasculature. Methods for quantifying perivascular adipose tissue in free-living populations will be described. Finally, the epidemiological literature demonstrating an association between perivascular adipose tissue and cardiometabolic disease will be explored.

Hypoxia enhances the relaxing influence of perivascular adipose tissue in isolated mice aorta

Adipose tissue releases an “adipocyte-derived relaxing factor” (ADRF) lowering tone of isolated arteries. The potential influence of hypoxia on the vasorelaxing properties of adipose tissue was investigated. Aortas from male Swiss mice with or without adherent adipose tissue were mounted in a wire myograph for isometric tension recording. Hypoxia (bubbling with 95% N 2, 5% CO 2) relaxed precontracted (norephinephrine, 5 μM) aorta with adipose tissue while only a minimal vasorelaxing effect was observed in arteries without adipose tissue. This effect was also seen after precontraction with prostaglandin F 2α (30 μM) or U-46619 (10 nM). Precontraction with 60 or 120 mM K +, incubation with tetraethylammoniumchloride (3 mM) or glibenclamide (30 μM) significantly impaired the hypoxic response. Glibenclamide (30 μM) enhanced the vasorelaxing effect of NaHS (except at high concentrations of NaHS). Lactate (10 nM to 1 mM) had no effect on preparations with or without adipose tissue. 8-(p-sulfophenyl)theophylline (0.1 mM), zinc protoporphyrin IX (10 μM), 1 H-[1, 2, 4]oxadiazolo[4,3-A]quinoxalin-1-one (10 μM) and removal of the endothelium did not influence the hypoxic relaxation. Our findings indicate that hypoxia has a relaxing influence on mice aorta that is dependent on the presence of adherent adipose tissue. This relaxation is partly mediated by opening K ATP channels and independent of the endothelium and soluble guanylyl cyclase. Neither lactate, adenosine, CO nor H 2S seems to be involved in this hypoxic response. However, the involvement of the as yet unidentified “adipocyte-derived relaxing factor” (ADRF) cannot be excluded.

Influence of Perivascular Adipose Tissue on Rat Aortic Smooth Muscle Responsiveness

Virtually every blood vessel in the body is surrounded to some degree by adipose tissue. A potential role for perivascular adipose tissue as a neurohumoral regulator of vascular responsiveness was studied. Thoracic aortae obtained from male Sprague-Dawley rats were cut into rings for use in a standard in vitro smooth muscle bath set-up. The vessels were either cleaned of surrounding adipose tissue or left intact. Contractile responses to KCl and phenylephrine as well as relaxation responses to acetylcholine, isoproterenol and sodium nitroprusside were not different between cleaned and intact tissues. However, a significant decrease in the sensitivity to norepinephrine was observed in intact vessels. This altered response was corrected by prior treatment with desipramine plus deoxycorticosterone. Contractile responses of aortic ring preparations to tyramine and a potassium-free physiological solution were significantly greater in intact tissues. Electrical stimulation resulted in no response in cleaned tissues, however, a frequency-dependent contraction was elicited in intact vessels. Phentolamine blocked the contractile responses generated by these manipulations which activate the sympathetic neuroeffector system. Responses evoked by electrical stimulation in intact vascular preparations were significantly attenuated by prior exposure to the selective angiotensin II (AII) antagonist SarI-Ile8-AII. These observations demonstrate that perivascular adipose tissue significantly influences vascular responsiveness in the in vitro setting.