Atherogenic Phenotype Research Articles

Effect of short-term reduced physical activity on cardiovascular risk factors in active lean and overweight middle-aged men

ObjectivesAn experimental reduction in physical activity is a useful tool for exploring the health benefits of physical activity. This study investigated whether similarly-active overweight men show a more pronounced response to reduced physical activity than their lean counterparts because of their atherogenic phenotype (i.e., greater abdominal adiposity). MethodsFrom 115 active men aged 45–64years, we recruited nine active lean (waist circumference <84cm) and nine active central overweight men (waist circumference >94cm). Fasting blood samples and responses to an oral glucose tolerance test (OGTT) were measured at baseline and following one week of reduced physical activity to simulate sedentary levels (removal of structured exercise and reduced habitual physical activity). ResultsGlucose and insulin areas under the curve (AUC), CRP, ALT, TAG were all higher in the overweight group and remained so throughout (P<0.05). Insulin and glucose AUC responses to an OGTT, as well as fasting triglyceride (TAG) concentrations, increased in both groups as a result of the intervention (P<0.05). There was no change in interleukin-6, C-reactive protein (CRP), Tumour Necrosis Factor-α, soluble intracellular adhesion molecule 1, or alanine transaminase (ALT). ConclusionOne-week of reduced activity similarly-impaired glucose control and increased fasting TAG in both lean and overweight men. Importantly, in spite of very similar (high) levels of habitual physical activity, central overweight men displayed a poorer profile for various inflammatory and metabolic outcomes (CRP, ALT, TAG, glucose AUC and insulin AUC).

Atherogenic low density lipoprotein phenotype in long-term survivors of childhood acute lymphoblastic leukemia

Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk of cardiovascular disease. Small density lipoproteins are atherogenic but have not been studied in this population. We conducted a cross-sectional analysis of 110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid subfractions were measured using Vertical Auto Profile-II. Participants with greater than 50% of LDL-cholesterol (LDL-c) in small dense LDL fractions (LDL(3+4)) were classified as LDL pattern B. Visceral and subcutaneous adipose tissue (VAT, SAT) volumes were also measured by computed tomography. While the mean LDL-c level of ALL survivors was 108.7 ± 26.8 mg/dl, 36% (40/110) of survivors had atherogenic LDL pattern B. This pattern was more common in males (26/47; 55%) than in females (14/63; 22%, P = 0.001) and more common in survivors treated with cranial radiotherapy (15/33; 45%) than in those who were treated with chemotherapy alone (25/77; 33%; P = 0.04, adjusted for age, gender, history of hypertension, and smoking history). VAT was associated with atherogenic lipids: LDL pattern B and LDL(3+4) levels. This association was independent of other measures of body fat. We conclude that a substantial proportion of ALL survivors had an atherogenic LDL phenotype despite normal mean LDL-c levels. An atherogenic LDL phenotype may contribute to the increase in cardiovascular mortality and morbidity in this population.

Effects of rosuvastatin versus pravastatin on low-density lipoprotein diameter in HIV-1-infected patients receiving ritonavir-boosted protease inhibitor

HIV infection is associated with an atherogenic lipoprotein profile, and ritonavir-boosted protease inhibitors exacerbate this phenotype. We evaluated the effect of 45 days of rosuvastatin versus pravastatin on the low-density lipoprotein (LDL) size and the distribution of LDL subfractions in HIV-1 patients receiving boosted protease inhibitors with elevated LDL levels. Substudy of the randomized double-blind multicentre ANRS 126 VIHstatine trial. Twenty clinical centres in France. HIV-infected patients receiving boosted protease inhibitors with dyslipidaemia (LDL cholesterol > 4.1 mmol/l and triglycerides < 8.8 mmol/l). Rosuvastatin 10 mg/day (n = 39) or pravastatin 40 mg/day (n = 37) for 45 days. LDL size and distribution of LDL subfractions blindly assessed by gradient gel electrophoresis at baseline and at day 45. Rosuvastatin was more effective than pravastatin in increasing the diameter of the LDL peak. The LDL diameter change was 0.33 ± 0.59 nm in the rosuvastatin group versus -0.01 ± 0.52 nm in the pravastatin group (P = 0.021). Rosuvastatin was also more effective in increasing significantly the percentage of large LDL (LDL1, P = 0.038; LDL2, P = 0.031) and in decreasing the percentage of small LDL (LDL3, P = 0.009). Rosuvastatin was more effective than pravastatin in normalizing LDL size and LDL subfraction distributions, leading to a less atherogenic phenotype.

LDL subclasses and lipoprotein-phospholipase A2 activity in suppressed HIV-infected patients switching to raltegravir: Spiral substudy

ObjectiveTo analyze the effect of switching the ritonavir-boosted protease inhibitor (PI/r) in a stable combined antiretroviral therapy (cART) regimen to raltegravir on low-density lipoprotein (LDL) particles, and lipoprotein-associated phospholipase A2 (Lp-PLA2). DesignSubstudy of a multicenter randomized trial that compared the efficacy of switching a PI/r to raltegravir-based cART in stable HIV-infected patients. MethodsLDL size and phenotype (by gel-gradient electrophoresis), Lp-PLA2 (by 2-thio-PAF [Cayman]), proprotein convertase subtilisin/kexin type 9 (PCSK9) (by ELISA), and standard lipid parameters were measured at baseline and week 48. ResultsEighty-one (PI/r n = 41 and raltegravir n = 40) patients were evaluated. No differences in baseline demographic and metabolic variables between arms were found except in apolipoprotein (Apo) B (p = 0.042). At week 48, total cholesterol (TC) (p < 0.001), LDL-c (p = 0.023), non-high density lipoprotein cholesterol non-high-density lipoprotein cholesterol (non-HDL-c) (p < 0.001), TC/HDL (p = 0.026), triglyceride (p < 0.001), Apo B (p < 0.001), Apo A-I (p = 0.004) and Lp (a) (p = 0.005) decreased in raltegravir arm compared to PI/r arm. At week 48, a shift from LDL phenotype B to the less atherogenic phenotype A was observed only in raltegravir arm (p < 0.001). LDL size increased (PI/r 2.1 nm, p = 0.019; raltegravir 3.8 nm, p = 0.001) and cholesterol content in small and dense LDL subfractions (LDL 4,5,6) decreased (PI/r p = 0.007, raltegravir p = 0.006) at week 48 in both arms. Total Lp-PLA2 activity (PI/r p = 0.037 and raltegravir p = 0.051) and PCSK9 plasma concentration decreased in both arms (PI/r p = 0.034 and raltegravir p < 0.001). ConclusionsSwitching a PI/r to a raltegravir-based cART in virologically suppressed HIV-infected patients was associated with an overall improvement in lipid profile, including a shift to a less atherogenic LDL phenotype.

Bad matters made worse

Heart attacks occur when lipoprotein-driven inflammation called atherosclerosis triggers blood clotting in the arteries. It seems that the attacks can, in turn, accelerate atherosclerosis by fanning the inflammation. See Letter p.325 Patients who have a myocardial infarction are at high risk of recurrent events. This study shows for the first time that myocardial infarction and stroke accelerate atherosclerosis. The authors were able to demonstrate that myocardial infarction leads to activation of the sympathetic nervous system, which, in turn, leads to the release of haematopoietic stem cells and progenitor cells. These cells seeded in the spleen and augmented the production of monocytes displaying an enhanced atherogenic phenotype. These findings were correlated with patient data showing that prior beta-blocker therapy was associated with a decrease in circulating monocytes after myocardial infarction. These findings suggest that interventions that interrupt the supply of monocytes could attenuate atherosclerosis and may improve long-term patient outcomes.

Elevation of Fatty Acid-Binding Protein 4 Is Predisposed by Family History of Hypertension and Contributes to Blood Pressure Elevation

BackgroundFatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, and atherosclerosis. However, little is known about the role of FABP4 in essential hypertension.MethodsWe first examined serum FABP4 concentrations in 18 normotensives (NT) and 30 nontreated essential hypertensives (EHT). The EHT were divided into 18 insulin-sensitive EHT (EHT-S) and 12 insulin-resistant EHT (EHT-R) based on their insulin-sensitivity index, the M value, determined by the hyperinsulinemic–euglycemic clamp technique. In the second study, we determined FABP4 levels in 30 young NT men with or without a family history of hypertension (FH+ and FH–, respectively; n = 15 each).ResultsSerum FABP4 level was significantly higher in the EHT-R than in the NT, whereas elevation of FABP4 level in the EHT-S was not statistically significant. FABP4 level was positively correlated with age, body mass index (BMI), blood pressure, and triglycerides and negatively correlated with the M value. FABP4 level was an independent predictor of mean arterial pressure after adjustment of age, gender, and adiposity. The FH+ group had a significantly lower level of M value and higher level of FABP4 than did the FH– group, and FABP4 concentration was an independent determinant of the M value.ConclusionsFABP4 contributes to blood pressure elevation and atherogenic metabolic phenotype in hypertensives, and the elevation of FABP4 is predisposed by a family history of hypertension.

Sleep Apnea Is Related to the Atherogenic Phenotype, Lipoprotein Subclass B

Sleep apnea has been implicated as an independent risk factor for atherosclerotic coronary artery disease (CAD). An association between the severity of sleep apnea and total cholesterol levels has previously been reported. However, the association with small dense low density lipoprotein (LDL) cholesterol concentration (subclass B), one of the strongest predictors of atherosclerosis, is unknown. We examined the relationship between sleep apnea and LDL subclass B, considering body size. This is a cross-sectional observational cohort of participants enrolled in a cardiovascular health study. Sleep apnea was assessed with a validated portable monitor. Lipid panels included total cholesterol, triglycerides, high density lipoprotein cholesterol, LDL cholesterol, and LDL subclasses A, B, and A/B. Sleep apnea was analyzed categorically using the apnea hypopnea index (AHI). A total of 519 participants were evaluated. Mean age was 58.7 ± 7.4 years; BMI was 29.6 ± 5.7; 65% were female; 59% were Caucasian, and 37% were African American. Among participants with abnormal waist circumference by ATP III criteria, moderate to severe sleep apnea (AHI ≥ 25) was not independently associated with LDL subclass B. In contrast, among participants with normal waist circumference, moderate to severe sleep apnea was associated with 4.5-fold odds of having LDL subclass B. Sleep apnea is independently associated with an atherogenic phenotype (LDL subclass B) in non-obese individuals. The association between sleep apnea and LDL subclass B in those with normal waist circumference may account, in part, for the increased risk of atherosclerosis and subsequent vascular events.

Shear‐responsive miR‐155 Regulates Endothelial Cell Phenotype and Function

In endothelial cells (ECs), unidirectional shear stress (USS) changes gene expression and promotes an atheroprotective cell phenotype, whereas low or oscillatory shear stress induces an atherogenic phenotype. We found that miR‐155 expression was increased 4 fold in response to USS, compared to oscillatory shear stress conditions. Transfection of miR‐155 mimic into human ECs dramatically altered the actin cytoskeleton organization. ECs overexpressing miR‐155 had less F‐ actin and less focal adhesions, indicated by a decrease in Vinculin and p‐FAK protein (p=0.016 and p=0.018). Furthermore, miR‐155 suppressed two key regulators of the EC cytoskeleton: RhoA (decreased 75%) and myosin light chain kinase (MYLK, decreased 40%). These miR‐ 155 mediated changes were associated with less EC migration (p=0.0106) and proliferation (p=0.0002). Also, ECs overexpressing miR‐155 showed less monocyte adhesion compared to control cells (p=0.0002). In vivo, miR‐155 expression was increased in the atheroprotected thoracic aorta (p=0.0012), where shear stress is unidirectional, compared to the atherosusceptible lower curvature of the aortic arch, where shear stress is low. In conclusion, we demonstrate that miR‐155 expression is regulated by shear‐stress in vitro and in vivo and suggest that miR‐155 induced changes in RhoA and MYLK expression are important for maintaining an atheroprotective phenotype in human ECs.

Chlamydia pneumoniae induces a pro-inflammatory phenotype in murine vascular smooth muscle cells independently of elevating reactive oxygen species

NADPH oxidases (Nox) are reactive oxygen species (ROS)-generating enzymes that play important physiological roles in host defence and redox signalling. However, Nox activity is upregulated in the vascular wall during atherosclerosis and contributes to plaque formation by promoting oxidative stress and inflammation. The bacterium Chlamydia pneumoniae has been detected in vascular smooth muscle cells (VSMC) of human atheroma. We hypothesized that C.pneumoniae infection of VSMC causes Nox activation, which initially limits infection but ultimately causes oxidative stress, activation of pro-inflammatory pathways and an atherogenic phenotype. Chlamydia pneumoniae infection of mouse cultured VSMC significantly increased ROS production by twofold but did not upregulate mRNA expression of Nox1 or Nox4. Chlamydia pneumoniae did increase Nox2 mRNA levels significantly by threefold, but this did not translate to elevated Nox2 protein expression. The Nox inhibitor gp91ds-tat had no effect on C.pneumoniae-induced ROS production. In contrast, apocynin significantly reduced ROS levels by 75% in C.pneumoniae-infected VSMC, an effect most likely attributable to its direct anti-oxidant action. Although apocynin had no effect on C.pneumoniae-induced expression of inflammatory markers, bacteria recovered from apocynin-treated VSMC displayed a higher degree of infectivity in HEp-2 cells. In conclusion, C.pneumoniae infection increases ROS production in VSMC independently of Nox activity. Although elevated ROS production appears to serve a protective role by limiting the spread of infection, we speculate that this response will be detrimental over the long term by causing oxidative stress and a smouldering inflammatory response by maintaining C.pneumoniae persistence within the cell.

Prevention and Treatment of Diabetic Retinopathy: Evidence from Large, Randomized Trials. The Emerging Role of Fenofibrate

Diabetic retinopathy (DR) remains a leading cause of preventable vision loss, despite advances in diabetes care. The burden of DR is likely to increase as the evolving pandemic of type 2 diabetes progresses. Tight control of blood glucose levels and blood pressure are essential for preventing or arresting the development of diabetic retinopathy, but are often difficult to achieve, and DR thus develops in a high proportion of patients. Current treatments for DR such as laser photocoagulation, intravitreous injections of corticosteroids or anti-vascular endothelial growth factor (VEGF) agents are indicated for advanced DR and have significant adverse effects. Therefore, new pharmacological treatments for the early stages of DR are needed. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial included a lipid management arm, in which patients satisfying additional inclusion criteria for the atherogenic dyslipidemia phenotype were randomly assigned to fenofibrate or placebo, each with a statin. In the ACCORD-EYE substudy, randomization to fenofibrate was associated with a significant reduction in the risk of progression of DR. These data confirm and extend the results of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, in which type 2 diabetes patients randomized to fenofibrate benefitted from a significantly lower incidence of laser treatment for retinopathy, progression of retinopathy or a composite measure of retinopathy outcomes. The results of ACCORD-EYE, together with those of FIELD, identify a place for fenofibrate for the prevention of retinopathy alongside intensive management of traditional risk factors, such as hyperglycemia and high blood pressure.

The effect of statins on high-risk atherosclerotic plaque associated with low endothelial shear stress

Low endothelial shear stress (ESS) plays an important role in the progression and severity of atherosclerotic lesions. As 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) appear to stabilize plaque, it would be valuable to understand how statins affect the nature of lesions in the proatherogenic and proinflammatory environment of low ESS and the effect of statins on that atherosclerotic process. The purpose of this review is to summarize the relationship among low ESS, high-risk plaque and statins. Low ESS is a critically important determinant of plaque development and progression to high-risk plaques with large necrotic lipid core, intensive inflammation and thin fibrous cap. In addition to the proatherogenic phenotypic switching in areas of low ESS, local LDL cholesterol concentrations are also increased in areas of low ESS, which exacerbates the local atherogenic process. In experimental models, statins appear to reduce the inflammation in lesions associated with low ESS and reduce the atherosclerotic phenotype even in these high-risk prone vascular areas. The relationship between low ESS and statins has not been fully investigated, but the available data underscore the vasculoprotective effect of statins. Understanding the mechanisms whereby statins reduce the atherogenic and inflammatory phenotype resulting from a low ESS environment would provide new insights to design strategies to prevent regional formation of high-risk, inflamed plaques likely to rupture and cause an adverse clinical event.

The association of serum prolactin concentration with inflammatory biomarkers – cross‐sectional findings from the population‐based Study of Health in Pomerania

Prolactin (PRL) is involved in immune regulation and may contribute to an atherogenic phenotype. Previous results on the association of PRL with inflammatory biomarkers have been conflicting and limited by small patient studies. Therefore, we used data from a large population-based sample to assess the cross-sectional associations between serum PRL concentration and high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6 (IL-6), and white blood cell (WBC) count. From the population-based Study of Health in Pomerania (SHIP), a total of 3744 subjects were available for the present analyses. PRL and inflammatory biomarkers were measured. Linear and logistic regression models adjusted for age, sex, body-mass-index, total cholesterol and glucose were analysed. Multivariable linear regression models revealed a positive association of PRL with WBC. Multivariable logistic regression analyses showed a significant association of PRL with increased IL-6 in non-smokers [highest vs lowest quintile: odds ratio 1·69 (95% confidence interval 1·10-2·58), P = 0·02] and smokers [OR 2·06 (95%-CI 1·10-3·89), P = 0·02]. Similar results were found for WBC in non-smokers [highest vs lowest quintile: OR 2·09 (95%-CI 1·21-3·61), P = 0·01)] but not in smokers. Linear and logistic regression analyses revealed no significant associations of PRL with hsCRP or fibrinogen. Serum PRL concentrations are associated with inflammatory biomarkers including IL-6 and WBC, but not hsCRP or fibrinogen. The suggested role of PRL in inflammation needs further investigation in future prospective studies.

Atherogenic Dyslipidemia in Patients With Transient Ischemic Attack

There is mounting evidence that atherogenic dyslipidemia (ie, low high-density lipoprotein cholesterol combined with high triglyceride concentrations) is an independent predictor of high cardiovascular risk and possibly of stroke. All patients included in the SOS-TIA cohort underwent an initial standardized evaluation, including medical history, physical examination, routine blood biochemistry, and diagnostic testing, and were followed for 1 year. Lipid profile was evaluated under fasting conditions. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol blood concentration ≤ 40 mg/dL and triglycerides ≥ 150 mg/dL. Among 1471 consecutive patients with transient ischemic attack (TIA) or minor stroke, overall prevalence of atherogenic dyslipidemia was 5.8%, but varied from 4.6% to 11.1%, depending on final diagnosis (possible TIA or TIA with a cerebral ischemic lesion, respectively). Prevalence of atherogenic dyslipidemia was independently associated with male sex, diabetes, and body mass index, but not with ABCD2 score. Atherogenic dyslipidemia also strongly associated with symptomatic intracranial stenosis ≥ 50% (adjusted odds ratio, 2.77; 95% CI, 1.38-5.55), but not with symptomatic extracranial stenosis ≥ 50% (adjusted odds ratio, 1.20; 95% CI, 0.64-2.26). Despite appropriate secondary prevention treatment, 90-day stroke risk was greater in patients with versus without atherogenic dyslipidemia (4.8% versus 1.7%; P=0.04). The atherogenic dyslipidemia phenotype in patients with TIA may be associated with intracranial artery stenosis and higher risk of early recurrent stroke. Additional data are needed to confirm these findings and to assess the best way to reduce important residual risk in such patients.

Non-dimensional coronary flow profiling: The new ace in the hole or a tool in search of an application?

Atherosclerosis remains the leading cause of morbidity and ortality in the western world [1]. It is usually regarded as systemic disease and several well-identified risk factors (i.e., ypertension, diabetes, hyperlipidemia, and cigarette smoking) ave been implicated in its pathogenesis. Noninvasive imaging of therosclerosis, such as intimal wall thickening and plaque formaion, is routinely available using a variety of imaging techniques. lthough the entire coronary tree is exposed to the effect of the ardiovascular risk factors, atherosclerotic lesions preferentially riginate in areas of disturbedflowassociatedwith low shear stress 2]. It has been shown that genes are differently expressed in areas f undisturbed and disturbed flow [3]. In vitro, shear stress high evels induce atheroprotective endothelial gene expression proles, while a shear stress low level stimulates the expression of n atherogenic phenotype [4]. Despite the increasing evidence that uid dynamical forces play a role in the expression of endothelial enes that are likely involved in atherogenesis, further investigaions are needed to rate these findings at their true value. More nsight into the level and the type of shear stress, and new diagnosic tools to establish the shear stress levels areparticularly required.

Fibrates Effect on Cardiovascular Risk Is Greater in Patients With High Triglyceride Levels or Atherogenic Dyslipidemia Profile: A Systematic Review and Meta-analysis

According to recently published data, fibrates may reduce the risk of major cardiovascular events. Whether patients with low high-density lipoprotein cholesterol (HDL-C), high triglyceride levels, or both may have additional benefits remains under debate.We performed a meta-analysis of the 5 large trials assessing the impact of fibrates on cardiovascular end points and providing information on low HDL-C and high triglyceride levels. Subgroups were determined according to values closest to predetermined cut-offs for both HDL-C and triglycerides (<35 and >200 mg/dL, respectively). Overall, 4671 patients (2401 in fibrate group and 2270 in placebo group) were classified as having an atherogenic dyslipidemia featuring low HDLC combined with high triglyceride levels. Across trials, the proportion of patients classified in this subgroup ranged from 11% to 33%. We found a significant difference in the magnitude of fibrate effect across dyslipidemia subgroups (P for between-group heterogeneity = 0.0002). A greater effect size was found in patients with high triglyceride levels or atherogenic dyslipidemia phenotype where fibrates were estimated to reduce the cardiovascular risk by 28% [95% confidence interval (CI), 15% to 39%; P < 0.001] or 30% (95% CI, 19% to 40%, P < 0.0001), respectively, but only by 6% (95% CI, 22% to 13%, P = 0.13) in nonatherogenic dyslipidemia patients. Targeting patients with high triglyceride levels or atherogenic dyslipidemia with fibrates may help reduce residual vascular risk.

What is the best predictor of the atherogenic LDL subclass phenotype ‘pattern B’ in patients with type 2 diabetes mellitus?

The atherogenic lipoprotein phenotype 'pattern B' comprises a predominance of small-dense low-density lipoprotein (sdLDL). Gradient gel electrophoresis (GGE) is considered a 'gold standard' method for identifying this phenotype, but is impractical for routine laboratory use. The low-density lipoprotein cholesterol:apolipoprotein-B (LDL-C:Apo-B) ratio has been advocated as a surrogate marker for sdLDL and a direct assay for sdLDL has recently become available. We compared the sdLDL assay and LDL-C:Apo-B with more established lipid parameters to predict the presence of 'pattern B' phenotype. Blood was collected from 97 fasted subjects on three separate occasions. Total cholesterol, triglyceride, Apo-B and sdLDL were measured; LDL- and HDL-cholesterol were determined after ultracentrifugation. The predominant LDL particle size and phenotype were assigned by GGE. 'Pattern B' phenotype was identified in 36% of samples. Peak particle size showed a positive correlation with HDL-cholesterol and a negative correlation with triglyceride and Apo-B. Receiver operating curve (ROC) analysis showed triglyceride:HDL-C ratio and triglyceride alone to be the best predictors of 'pattern B' phenotype, with area under the curve (AUC) being 0.87 and 0.84, respectively. AUCs for sdLDL (0.74) and LDL-C:Apo-B (0.71) were significantly lower (P < 0.05). A high sdLDL concentration had the greatest specificity (95%) and positive predictive value (74%) for 'pattern B' phenotype, but low sensitivity (43%). Direct measurement of sdLDL provided the most specific predictor of 'pattern B' phenotype, whereas triglyceride:HDL-C ratio or triglycerides alone, parameters readily available in most laboratories, were the best predictors by ROC analysis.

Prevalence of LDL atherogenic phenotype in patients with systemic lupus erythematosus.

Background:Patients with systemic lupus erythematosus (SLE) are 5–8 times more likely to develop coronary heart disease than the general population. The aim of this study was to find out the prevalence of the small dense low-density lipoprotein (LDL) cholesterol particle in patients with SLE.Methods:We recruited 50 consecutive patients with SLE who had no evidence of hypertension or renal failure. Fifty age- and gender-matched healthy controls were also recruited. We measured serum lipid levels and LDL particle diameters by gradient gel electrophoresis in both patients and controls.Results:Patients with SLE had significant dyslipidemia, characterized by elevated plasma triglycerides, LDL cholesterol, Apoprotein B, triglyceride:high-density (HDL) lipoprotein cholesterol ratio, and decreased plasma concentrations of HDL cholesterol. The LDL particle size in SLE (24.8 ± 1.23 nm) was significantly (P < 0.01) smaller than that in controls (26.1 ± 1.31 nm). The prevalence of the LDL phenotype B (the atherogenic phenotype) was 52% in SLE but only 20% in healthy controls.Conclusion:We conclude that the high prevalence of small dense LDL in SLE may contribute to the high incidence of coronary heart disease seen in this disorder.

L’inflammation postprandiale : les données récentes suggèrent un rôle préventif des protéines alimentaires et de leur nature

It is now well known that a high-energy meal that is rich in saturated fat and sugars induces the transient appearance of some metabolic dysregulations and inflammatory-related phenomena in the postprandial state, in close association with the increase in plasma triglycerides and glucose. Documented features of postprandial inflammation include the increase in plasma inflammatory markers related to the systemic level (e.g. proinflammatory cytokines) or the vascular endothelium (e.g. adhesion molecules), the activation of blood leucocytes, and different physiological markers of ‘‘endothelial dysfunction’’, which relates to the transition of the endothelium toward a pro-inflammatory atherogenic phenotype. The role of fat and carbohydrates in postprandial inflammation has been much studied, while the impact of dietary protein has been overlooked. The present review will focus on the few recent studies that have examined the effect of dietary protein, and different dietary protein sources, on postprandial inflammation and reported a favorable impact on endothelial function. The literature also showed that arginine and cysteine are important amino acids in mediating these effects. Some further studies in this setting are warranted to better characterize and analyze the potential benefit of different dietary protein sources for cardiovascular risk.

The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis?

Atherosclerotic vascular disease is the consequence of a chronic inflammatory process, and prolactin has been shown to be a component of the inflammatory response. Additionally, recent studies indicate that prolactin contributes to an atherogenic phenotype. We hypothesized that this may be the result of a direct effect of prolactin on atherogenesis through activation of the prolactin receptor. Human carotid atherosclerotic plaques were obtained from patients by endarteriectomies. The mRNA of prolactin receptor, but not of prolactin, was detected in these atherosclerotic plaques by quantitative real-time PCR. In situ hybridization confirmed the expression of the prolactin receptor in mononuclear cells. Analysis at the protein level using immunohistochemistry and immunoelectron microscopy revealed that the prolactin receptor was abundantly present in macrophages near the lipid core and shoulder regions of the plaques. Our findings demonstrate that the prolactin receptor is present in macrophages of the atherosclerotic plaque at sites of most prominent inflammation. We therefore propose that prolactin receptor signaling contributes to the local inflammatory response within the atherosclerotic plaque and thus to atherogenesis.

Prolactin is Involved in the Systemic Inflammatory Response in Myocardial Infarction

Prolactin may contribute to an atherogenic phenotype. Furthermore, previous studies have shown that prolactin levels increase in situations of acute stress and inflammation. We therefore aimed to investigate the relationship between prolactin, acute stress and inflammation in patients with myocardial infarction. We performed a case-control study in 40 patients with myocardial infarction and 39 controls, aged 41-84 years. Blood for assessment of prolactin and high sensitive C-reactive protein (hsCRP) was drawn at inclusion, that is, during the acute phase of the event, and 2-3 weeks later. Unexpectedly, prolactin levels at inclusion did not differ between cases and controls (7.0 ng/ml and 6.0 ng/ml, respectively, p=0.28). 2-3 weeks later prolactin levels in cases had not decreased. However, univariate regression analysis indicated that hsCRP is associated with prolactin levels (regression coefficient β 0.11; [95% CI 0.01; 0.21]; p=0.03) in cases during the acute phase of myocardial infarction. Our findings may suggest that prolactin is involved in the systemic inflammatory response, which takes place during myocardial infarction; however, this association may not be strong enough to induce higher prolactin levels in patients with myocardial infarction.