FcγRIIb levels | 26 patients with biopsy-proven NAFLD | FcγRIIb expression levels correlated negatively with serum lipids, type 4 collagen and hyaluronic acid, which are involved in hepatic lipid metabolism disorder, fibrosis, and inflammation | Ishikawa T et al., 201973 |
AGTR1 rs5186 A1166C variant, adipokine profile, inflammatory and ED markers, plasma lipoproteins, glucose, adipokines, MCP-1, calprotectin, and nuclear factor-κB activation in circulating mononuclear cells | 78 biopsy-proven non-diabetic NAFLD patients and 314 controls | AGTR1 A1166C variant affects liver disease, IR, and ED in NAFLD, predicting a 9-year increase in CV disease risk and ED markers | Musso G et al., 201974 |
Serum SelP levels, CIMT, FMD | 93 patients with NAFLD (n=29 biopsy proven, n=64 proven by US staging) and 37 healthy controls | NAFLD patients had higher SelP, lower FMD and similar CIMT compared with controls. SelP, ESR and CRP were significantly higher and FMD lower in NASH compared with simple steatosis. FMD may be a better predictor for assessment of CVD risk when compared with cIMT | Cetindağlı I et al., 201775 |
VCAM-1, placental growth factor, endoglin, vascular endothelial-cadherin | Obese male with biopsy-confirmed NAFLD patients undergoing bariatric surgery (n=61) and control patients (n=35) | Vascular endothelial-cadherin levels were higher and placental growth factor lower in NAFL and NASH patients compared to the controls. VCAM-1 was the only variable independently associated with significant fibrosis (>F2). VCAM-1 levels were able to accurately predict significant (>F2) fibrosis in NAFLD patients | Lafere S et al., 201776 |
Platelet-derived phosphorylated-eNOS (p-eNOS), hepatic p-eNOS, FMD | 54 biopsy-confirmed NAFLD patients (38,8% patients had NAFL and 61,7% NASH) | In NAFLD there was an impairment of eNOS and NAFL showed a higher impairment of eNOS phosphorylation in comparison to NASH (p < 0.01). The vascular response by FMD was worse in NASH as compared with NAFL. eNOS dysfunction observed in platelets and liver tissue did not match FMD | Persico M et al., 201777 |
FMD, oxidative stress (Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx)) | 19 biopsy-proven NASH patients, 19 NAFLD patients and 19 controls without signs of steatosis | NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH compared to controls. Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients | Loffredo L et al., 201778 |
ED (strain-gauge plethysmography) after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside | 272 hypertensive patients with MS (consisting 93 NAFLD patients detected by calculating the noninvasive FLI) | MS and NAFLD hypertensive group showed a worse endothelium-dependent vasodilation compared with MS without NAFLD. NAFLD may be an early marker of ED in hypertensive’s | Perticone M et al., 201679 |
Brachial FMD | 176 patients with US evaluated liver steatosis and 90 controls | Patients with grade 3 steatosis had significantly lower FMD values than those with grade 1 steatosis and controls. ED was associated with steatosis in patients with NAFLD | Sapmaz F et al., 201672 |
PTX-3, ADMA, adiponectin, and hs-CRP | 70 patients with biopsy-proven NAFLD and 70 healthy controls | Increased circulating PTX-3 was strongly associated with ED in subjects with NAFLD | Gurel H et al., 201680 |
CIMT, FMD, pulse wave velocity measurement | 61 male biopsy-proven NAFLD patients and 41 controls | NASH and NAFLD (with and without MS) patients had decreased FMD, increased CIMT and pulse wave velocity measurement than controls. NAFLD leads to increased risk of ED and atherosclerosis in adult male patients, independent of MS | Ozturk K et al., 201581 |
ED (photoplethysmography), caspase-8 | 76 patients: 43 with MS (72.1% of them with NAFLD) and 33 controls | NAFLD patients had higher arterial stiffness, longer systolic duration, more pronounced ED. Higher caspase-8 levels may serve as a prognostic marker for the development of CVD and NAFLD | Drapkina OM et al., 201582 |
FMD, peripheral arterial tonometry ratio, carotid-femoral pulse wave velocity | 2,284 Framingham Heart Study participants without overt CVD (15,3% had NAFLD diagnosed with liver fat attenuation measured on computed tomography) | Greater liver fat was modestly associated with lower FMD, lower peripheral arterial tonometry ratio, higher carotid-femoral pulse wave velocity and higher mean arterial pressure | Long MT et al., 201583 |
Brachial FMD | 34 obese NAFLD patients (confirmed by MR imaging and spectroscopy) and 20 obese controls | NAFLD patients exhibited impaired FMD compared with controls, but could be improved by exercise training | Pugh CJ et al., 201484 |
Fingertip pneumo-optic plethysmography in OSA patients | 139 NAFLD (OSA) patients and 87 OSA patients (noninvasive blood tests were used to evaluate NAFLD- SteatoTest, NashTest, and FibroTest) | ED was more prominent in moderate or severe steatosis and borderline or possible NASH. The severity of nocturnal hypoxia was independently associated with steatosis. Preexisting obesity exacerbated the effects of nocturnal hypoxemia. NAFLD is a potential mechanism of ED in OSA | Minville C et al., 201485 |
Endocan and high mobility group box 1 (ELISA), anti-endothelial cell antibodies (flow cytometry) | 77 patients with US and/or fatty liver index diagnosed NAFLD | Severity of coronary artery disease in NAFLD positively correlated with endocan and negatively with high mobility group box 1 levels. Anti-endothelial cell antibodies were not significantly associated with coronary artery disease in NAFLD | Elsheikh E et al., 201486 |
Serum VCAM-1, ICAM-1, MPO, adiponectin, PAI-1, SAP, SAA, E-selectin, and MMP-9 | 44 patients one year after liver transplantation compared to 22 biopsy-proven NASH patients and controls | Liver transplant patients and NASH patients had similar inflammatory and endothelial serum markers compared to the controls, lower IL-10 levels and higher IFNγ, E-selectin, serum VCAM-1 and ICAM-1 levels | Alvares-da-Silva MR et al., 201487 |
Serum ICAM-1, endothelin-1 (ET-1), CIMT, brachial-ankle pulse wave velocity and ankle-brachial index | 51 patients with biopsy-proven NAFLD | Serum levels of hs-CRP, sICAM-1, ET-1, CIMT and brachial-ankle pulse wave velocity were significantly higher in the NASH group than the NAFL group | Cao Y et al., 201488 |
ADMA, brachial FMD | 100 patients with NAFLD (US and fatty liver index, biopsy when available) | There was no significant difference in the serum ADMA concentration or FMD between the NAFLD and control groups | Sayki Arslan M et al., 201489 |
Fetuin-A, ADMA, adiponectin, carotid atherosclerosis (cIMT) | 115 patients with NAFLD (biopsy and US proven) and 74 healty controls | NAFLD group had higher fetuin-A, ADMA and cIMT, and lower adiponectin than control. Circulating fetuin-A in NAFLD was independently associated with ED and subclinical atherosclerosis | Dogru T et al., 201390 |
Brachial and carotid artery FMD and CIMT | 50 biopsy-proven NASH patients and 30 healthy controls | In patients with NASH, serum concentrations of GGT and ALT might have a predictive value for FMD and CIMT | Arinc H et al., 201391 |
Endothelial progenitor cells | 20 NAFLD patients (according to the degree of steatosis measured by US) and 20 individuals without NAFLD selected from the control group (n=96) | NAFLD group had increased levels of endothelial progenitor cells. Endothelial progenitor cells were associated with the severity of NAFLD | Gutiérrez-Grobe Y et al., 201392 |
FMD, CIMT, lipids, insulin, C-peptide, and fasting blood glucose, HOMA-IR | 161 patient, 117 US defined NAFLD patients | NAFLD is associated with impaired CIMT and FMD, which are early markers of atherosclerosis | Kucukazman M et al., 201393 |
SREBF-2 polymorphism, endothelial adhesion molecules, plasma lipoproteins, adipokines, and cytokeratin-18 fragments | 175 non-obese, non-diabetic participants without NAFLD or MS and NAFLD patients with liver biopsy | SREBF-2 polymorphism predisposes individuals to NAFLD and associated cardio-metabolic abnormalities. It also affects liver histology and glucose and lipid metabolism in NAFLD | Musso G et al., 201394 |
Plasma ADMA, FMD, CIMT | 51 biopsy-confirmed NAFLD patients and 21 controls | CIMT increase and FMD decrease was independent from MS and more evident in simple steatosis and NASH compared to controls. ADMA levels showed no significant difference in NAFLD and controls. NAFLD was associated with ED and increased earlier in patients with atherosclerosis compared to control subjects | Colak Y et al., 201395 |
Plasma triglyceride-rich lipoproteins, oxidized low-density lipoproteins, adipokines, and cytokeratin-18 fragments | 40 non-obese, non-diabetic, normolipidemic biopsy-proven NAFLD patients and 40 healthy subjects | Adipose IR, endothelial adhesion molecules, and hepatic IR progressively increased across NAFLD stages as well as cardio-metabolic parameters | Musso G et al., 201296 |
OGTT fasting and 2 h, insulin, lipid profile, C-reactive protein, sICAM-1, VCAM-1, CIMT, FMD | 40 NAFLD patients (fatty liver assessed by US) and 40 controls | NAFLD patients had a significantly greater degree of impairment in FMD, CIMT and higher levels of hs-CRP and sICAM-1. NAFLD was significantly associated with subclinical atherosclerosis and ED independent of obesity and MS | Thakur ML et al., 201297 |
Plasma ADMA, glucose, lipids and insulin, HOMA-IR, CIMT | 67 non-diabetic and normotensive biopsy-confirmed NAFLD patients and 35 healthy controls | Plasma ADMA levels were increased in subjects with NAFLD, independent from IR, liver histology and CV risk factors. Circulating ADMA may be an earlier marker of vascular damage with respect to CIMT in subjects with NAFLD | Dogru T et al., 201298 |
Bone marrow-derived-endothelial progenitor cells | 34 patients with US assessed NAFLD and 68 controls with suspected coronary artery disease | NAFLD patients had significantly decreased circulating endothelial progenitor cell levels, attenuated endothelial progenitor cell functions, and enhanced systemic inflammation compared to controls | Chiang CH et al., 201299 |
CIMT, brachial FMD | 84 patients with US defined NAFLD and 65 controls | Brachial FMD was significantly reduced in patients with NAFLD | Mohammadi A et al., 2011100 |
HOMA-IR, inflammatory adipokine score (IL-6, serum amyloid A, ICAM, adiponectin, and leptin), ED score (E-selectin, vascular cell adhesion molecule, vWF), and plasma levels of NEFA | 434 subjects from the Cohort on Diabetes and Atherosclerosis Maastricht study. NAFLD diagnosed by increased ALT levels | IR, ED and NEFA, but not the MS or inflammatory adipokines, were significantly associated with plasma ALT. IR constitutes a key pathophysiological link between the MS and NAFLD, which may operate through adipose tissue-associated inflammation and ED and to a lesser extent through nonesterified fatty acids | Jacobs M et al., 2011101 |
Brachial FMD, hs-CRP, hs-IL6 and cell adhesion molecules, hepatocellular lipids, visceral and subcutaneous fat (MR spectroscopy) | 28 obese children with NAFLD (MR spectroscopy elevated hepatic lipid content) compared with obese children with normal liver fat content | Increased hepatocellular lipid content was positively correlated to higher serum levels of hs-CRP and hs-IL6. No difference was found in vCAM and iCAM or FMD between groups | Weghuber D et al., 2011102 |
Endothelium-dependent vasodilation | 40 hypertensive patients with laboratory and US proven NAFLD | Endothelium-dependent vasodilation was significantly reduced in hypertensive patients with NAFLD in comparison with hypertensive patients without NAFLD | Sciacqua A et al., 2011103 |
CIMT, carotid-femoral pulse wave velocity and FMD | 23 biopsy-confirmed NAFLD patients and 28 controls subjects | NAFLD subjects had significantly higher carotid-femoral pulse wave velocity, CIMT and reduced FMD. NAFLD was associated with arterial stiffness and ED | Vlachopoulos C et al., 2010104 |
HOMA-IR >2, oxidative stress, soluble adhesion molecules (ICAM-1, VCAM-1 and E-selectin), and circulating adipokines (TNF-α, leptin, adiponectin, and resistin) | 197 non-obese non-diabetic subjects (population-based cohort), NAFLD was assessed with US and elevated ALT (≥30 units/l in men and ≥20 units/l in women), 66% had liver biopsy | NAFLD independently predicted HOMA-IR, nitrotyrosine, and soluble adhesion molecules on logistic regression analysis. NAFLD was tightly associated with IR and markers of oxidative stress and ED and may help identify individuals with increased cardio-metabolic risk | Musso G et al., 2008105 |
Brachial endothelial-dependent dilatation (reactive hyperaemia), and endothelial-independent dilatation (sublingual nitrate) | 15 NASH and 17 simple steatosis biopsy-confirmed NAFLD patients and 16 healthy subjects | Patients with NASH had worse ED compared with patients with simple steatosis and healthy subjects | Senturk O et al., 2008106 |
Immunoperoxidase stains for alpha-smooth muscle actin and CD31 | Liver biopsies from 62 NAFLD patients, 21 HBV, and 19 HCV patients | CD31 was a marker of endothelial damage and sinusoidal capillary transformation particularly in NAFLD | Akyol G et al., 2005107 |
Flow-mediated vasodilation (FMV) | 52 NAFLD cases (ALT≥1,5 ULN and US) and 28 age- and sex-matched controls | FMV was lower in NAFLD vs. controls and more pronounced in steatohepatitis than in simple fatty liver. The defect had to reside at the endothelium level because no differences were observed in flow-independent vasodilation | Villanova N et al., 2005108 |