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Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

ABSTRACT: BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (? = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (? = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (? = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.

SUBMITTER: Sajja A

PROVIDER: S-EPMC7710282 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

Sajja Aparna A Abdelrahman Khaled M KM Reddy Aarthi S AS Dey Amit K AK Uceda Domingo E DE Lateef Sundus S SS Sorokin Alexander V AV Teague Heather L HL Chung Jonathan J Rivers Joshua J Joshi Aditya A AA Elnabawi Youssef A YA Goyal Aditya A Rodante Justin A JA Keel Andrew A Alvarez Julie E JE Lockshin Benjamin B Prussick Ronald R Siegel Evan E Playford Martin P MP Chen Marcus Y MY Bluemke David A DA Gelfand Joel M JM Mehta Nehal N NN

JCI insight 20201119 22

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT t ...[more]

PMID: 33104056

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Project description:BackgroundAs for the coronary artery inflammation and coronary atherosclerotic burden, which are used to assess the risk of adverse cardiac events in patients, it is unclear whether there is any certain correlation between them. Therefore, the purpose of this study was to explore the potential relationship between coronary artery inflammation and coronary atherosclerotic burden.MethodsA total of 346 eligible patients underwent assessment of computed tomography (CT) attenuation values of pericoronary adipose tissue (PCAT) in the right coronary artery and Agatston coronary artery calcium (CAC) based on coronary CT angiography. These measurements were utilized to evaluate coronary inflammation and atherosclerotic burden, respectively. Patients with a CAC score of 0 were categorized into groups based on the presence or absence of coronary artery disease (CAD). CAC scores of 10, 100, and 400 were chosen as cutoff values to compare differences in PCAT attenuation values across different CAC scores.ResultsWhen comparing all CAD patients to non-CAD patients, a significantly higher PCAT attenuation was observed in CAD patients (-87.54±9.39 vs. -93.45±7.42 HU, P=0.000). The PCAT attenuation in CAD patients with a CAC score of 0 was significantly higher than that in patients with a CAC score greater than 0 and in non-CAD patients with a CAC score of 0 (-82.63±8.70 vs. -90.38±8.59 vs. -93.45±7.42 HU, P=0.000). The PCAT attenuation values did not exhibit significant differences among different CAC scores (all P>0.05); however, it was highest in CAD patients with a CAC score of 0 (P<0.05). Body mass index, hyperlipidemia, hypertension, and PCAT attenuation were identified as independent risk factors in both CAD patients with a CAC score of 0 and patients with a CAC score greater than 0 (all P<0.05).ConclusionsThe results of this study suggest that a direct relationship between coronary inflammation and coronary atherosclerotic burden is not evident. Nonetheless, it is noteworthy that coronary inflammation was most pronounced in CAD patients with a CAC score of 0, while CAC score did not demonstrate an association with inflammation.

Project description:ImportanceInflammation is critical to atherosclerosis. Psoriasis, a chronic inflammatory disease associated with early cardiovascular events and increased aortic vascular inflammation (VI), provides a model to study the process of early atherogenesis. Fludeoxyglucose F 18 positron emission tomography/computed tomography (18F-FDG PET/CT) helps quantify aortic VI, and coronary computed tomography angiography provides coronary artery disease (CAD) assessment through evaluation of total plaque burden (TB) and noncalcified coronary plaque burden (NCB), luminal stenosis, and high-risk plaques (HRP). To our knowledge, association between aortic VI and broad CAD indices has not yet been assessed in a chronic inflammatory disease state. Such a study may provide information regarding the utility of aortic VI in capturing early CAD.ObjectiveTo assess the association between aortic VI and CAD indices, including TB, NCB, luminal stenosis, and HRP prevalence, in psoriasis.Design, setting, and participantsIn a cross-sectional cohort study at the National Institutes of Health, 215 consecutive patients with psoriasis were recruited from surrounding outpatient dermatology practices. All patients underwent 18F-FDG PET/CT for aortic VI assessment, and 190 of 215 patients underwent coronary computed tomography angiography to characterize CAD. The study was conducted between January 1, 2013, and May 31, 2017. Data were analyzed in March 2018.ExposuresAortic VI assessed by 18F-FDG PET/CT.Main outcomes and measuresPrimary outcome: TB and NCB. Secondary outcomes: luminal stenosis and HRP.ResultsAmong 215 patients with psoriasis (mean [SD] age, 50.4 [12.6] years; 126 men [59%]), patients with increased aortic VI had increased TB (standardized β = 0.48; P < .001), and higher prevalence of luminal stenosis (OR, 3.63; 95% CI, 1.71-7.70; P = .001) and HRP (OR, 3.05; 95% CI, 1.42-6.47; P = .004). The aortic VI and TB association was primarily driven by NCB (β = 0.49; P < .001), whereas the aortic VI and HRP association was driven by low-attenuation plaque (OR, 5.63; 95% CI, 1.96-16.19; P = .001). All associations of aortic VI remained significant after adjustment for cardiovascular risk factors: aortic VI and TB (β = 0.23; P < .001), NCB (β = 0.24; P < .001), luminal stenosis (OR, 3.40; 95% CI, 1.40-8.24; P = .007), and HRP (OR, 2.72; 95% CI, 1.08-6.83; P = .03). No association was found between aortic VI and dense-calcified coronary plaque burden.Conclusions and relevanceAortic VI is associated with broad CAD indices, suggesting that aortic VI may be a surrogate for early CAD. Larger prospective studies need to assess these associations longitudinally and examine treatment effects on these outcomes.

Project description:Poly(ADP-ribose) polymerase 2 (PARP2) alongside PARP1 are responsible for the bulk of cellular PARP activity, and they were first described as DNA repair factors. However, research in past decades implicated PARPs in biological functions as diverse as the regulation of cellular energetics, lipid homeostasis, cell death, and inflammation. PARP activation was described in Th2-mediated inflammatory processes, but studies focused on the role of PARP1, while we have little information on PARP2 in inflammatory regulation. In this study, we assessed the role of PARP2 in a Th17-mediated inflammatory skin condition, psoriasis. We found that PARP2 mRNA expression is increased in human psoriatic lesions. Therefore, we studied the functional consequence of decreased PARP2 expression in murine and cellular human models of psoriasis. We observed that the deletion of PARP2 attenuated the imiquimod-induced psoriasis-like dermatitis in mice. Silencing of PARP2 in human keratinocytes prevented their hyperproliferation, maintained their terminal differentiation, and reduced their production of inflammatory mediators after treatment with psoriasis-mimicking cytokines IL17A and TNFα. Underlying these observations, we found that aromatase was induced in the epidermis of PARP2 knock-out mice and in PARP2-deficient human keratinocytes, and the resulting higher estradiol production suppressed NF-κB activation, and hence, inflammation in keratinocytes. Steroidogenic alterations have previously been described in psoriasis, and we extend these observations by showing that aromatase expression is reduced in psoriatic lesions. Collectively, our data identify PARP2 as a modulator of estrogen biosynthesis by epidermal keratinocytes that may be relevant in Th17 type inflammation. KEY MESSAGES : PARP2 mRNA expression is increased in lesional skin of psoriasis patients. PARP2 deletion in mice attenuated IMQ-induced psoriasis-like dermatitis. NF-κB activation is suppressed in PARP2-deficient human keratinocytes. Higher estradiol in PARP2-deficient keratinocytes conveys anti-inflammatory effect.

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Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

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Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

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