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Circulating serum fatty acid synthase is elevated in patients with diabetes and carotid artery stenosis and is LDL-associated.

ABSTRACT: BACKGROUND AND AIMS:Diabetes is an independent risk factor for carotid artery stenosis (CAS). Fatty acid synthase (FAS), an essential de novo lipogenesis enzyme, has increased activity in the setting of diabetes that leads to altered lipid metabolism. Circulating FAS (cFAS) was recently observed in the blood of patients with hyperinsulinemia and cancer. We thought to evaluate the origin of cFAS and its role in diabetes-associated CAS. METHODS:Patients with diabetes and no diabetes, undergoing carotid endarterectomy (CEA) for CAS, were prospectively enrolled for collection of plaque and fasting serum. FPLC was used to purify lipoprotein fractions, and ELISA was used to quantify cFAS content and activity. Immunoprecipitation (IP) was used to evaluate the affinity of cFAS to LDL-ApoB. RESULTS:Patients with CAS had higher cFAS activity (p?

SUBMITTER: De Silva GS

PROVIDER: S-EPMC6707847 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Circulating serum fatty acid synthase is elevated in patients with diabetes and carotid artery stenosis and is LDL-associated.

De Silva Gayan S GS Desai Kshitij K Darwech Malik M Naim Uzma U Jin Xiaohua X Adak Sangeeta S Harroun Nikolai N Sanchez Luis A LA Semenkovich Clay F CF Zayed Mohamed A MA

Atherosclerosis 20190530

<h4>Background and aims</h4>Diabetes is an independent risk factor for carotid artery stenosis (CAS). Fatty acid synthase (FAS), an essential de novo lipogenesis enzyme, has increased activity in the setting of diabetes that leads to altered lipid metabolism. Circulating FAS (cFAS) was recently observed in the blood of patients with hyperinsulinemia and cancer. We thought to evaluate the origin of cFAS and its role in diabetes-associated CAS.<h4>Methods</h4>Patients with diabetes and no diabetes ...[more]

PMID: 31202106

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Project description:BACKGROUND:Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS:This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (>?70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2?days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. RESULTS:The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r?=?0.42 P?=?.02) and with 18F-FDG uptake (r?=?0.38 P?=?.05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077?days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR?=?1.15 P?=?.006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. CONCLUSIONS:Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.

Dataset Information

Circulating serum fatty acid synthase is elevated in patients with diabetes and carotid artery stenosis and is LDL-associated.

Publications

Circulating serum fatty acid synthase is elevated in patients with diabetes and carotid artery stenosis and is LDL-associated.

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