Cholesterol in the Cell Membrane-An Emerging Player in Atherogenesis.

Membrane cholesterol is essential for cell membrane properties, just as serum cholesterol is important for the transport of molecules between organs. This review focuses on cholesterol transport between lipoproteins and lipid rafts on the surface of macrophages. Recent studies exploring this mechanism and recognition of the central dogma-the key role of macrophages in cardiovascular disease-have led to the notion that this transport mechanism plays a major role in the pathogenesis of atherosclerosis. The exact molecular mechanism of this transport remains unclear. Future research will improve our understanding of the molecular and cellular bases of lipid raft-associated cholesterol transport.

The relationship between non-HDL cholesterol and macrophage phenotypes in human adipose tissue.

Data from experimental animal models and in vitro studies suggest that both hyperlipoproteinemia and obesity predispose to development of proinflammatory pathways of macrophages within adipose tissue. The aim of this study was to analyze whether non-HDL cholesterol concentration in healthy living kidney donors (LKDs) is related to the number and phenotype of proinflammatory macrophages in visceral and subcutaneous adipose tissue. Adipose tissue samples were collected by cleansing the kidney grafts of LKDs obtained peroperatively. The stromal vascular fractions of these tissues were analyzed by flow cytometry. Proinflammatory macrophages were defined as CD14+ cells coexpressing CD16+ and high-expression CD36 as well (CD14+CD16+CD36+++), while CD16 negativity and CD163 positivity identified alternatively stimulated, anti-inflammatory macrophages. Non-HDL cholesterol concentration positively correlated to proinflammatory macrophages within visceral adipose tissue, with increased strength with more precise phenotype determination. On the contrary, the proportion of alternatively stimulated macrophages correlated negatively with non-HDL cholesterol. The present study suggests a relationship of non-HDL cholesterol concentration to the number and phenotype proportion of macrophages in visceral adipose tissue of healthy humans.

Characterisation and comparison of adipose tissue macrophages from human subcutaneous, visceral and perivascular adipose tissue.

BACKGROUND AND AIMS: Macrophages play important roles in adipose tissue inflammation and its consequences. Unfortunately, a detailed description of the macrophage phenotypes in different human adipose tissues is not available. SUBJECTS AND METHODS: Subcutaneous, visceral and perivascular adipose tissues were obtained from 52 living kidney donors during live donor nephrectomy. Stromal vascular fractions were isolated, and the macrophage phenotypes were analyzed by flow cytometry using surface markers (CD14, CD16, CD36, and CD163). RESULTS: In addition to CD16 positivity, pro-inflammatory macrophages also display high scavenger receptor CD36 expression. The great majority of CD16 negative macrophages express the anti-inflammatory CD163 marker. The presence of pro-inflammatory macrophages was almost twice as high in visceral (p < 0.0001) and perivascular (p < 0.0001) adipose tissues than in subcutaneous tissue. This difference was substantially more pronounced in the postmenopausal women subgroup, consequentlly, the total difference was driven by this subgroup. CONCLUSION: We obtained detailed information about M1 and M2 macrophage phenotypes in human adipose tissue. The visceral and perivascular adipose tissues had substantially higher pro-inflammatory characteristics than the subcutaneous tissue. The higher proportion of pro-inflammatory macrophages in the visceral adipose tissue of postmenopausal women might be related to an increased cardiovascular risk.

Endothelial progenitor cells and asymmetric dimethylarginine after renal transplantation.

Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 µmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 µmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx.

Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

Exposing and exploiting host-parasite arms race clues in SARS-CoV-2: a principally new method for improved T cell immunogenicity prediction.

Computational prediction of T cell epitopes is a crucial component in the development of novel vaccines. T cells in a healthy vertebrate host can recognize as non-self only those peptides that are present in the parasite's proteins but absent in the host's proteins. This principle enables us to determine the current and past host specificity of a parasite and to predict peptides capable of eliciting a T cell response. Building upon the detailed mapping of T cell clone specificity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigens, we employed Monte Carlo tests to determine that empirically confirmed T cell-stimulating peptides have a significantly increased proportion of pentapeptides, hexapeptides and heptapeptides not found in the human proteome (P < 0.0001, Cohen's d > 4.9). We observed a lower density of potential pentapeptide targets for T cell recognition in the spike protein from the human-adapted SARS-CoV-2 ancestor compared to 10 other SARS-CoV-2 proteins originating from the horseshoe bat-adapted ancestor. Our novel method for predicting T cell immunogenicity of SARS-CoV-2 peptides is four times more effective than previous approaches. We recommend utilizing our theory-based method where efficient empirically based algorithms are unavailable, such as in the development of certain veterinary vaccines, and combining it with empirical methods in other cases for optimal results.

Alcoholic chronic pancreatitis and liver cirrhosis: coincidence and differences in lifestyle.

BACKGROUND/OBJECTIVES: Alcoholic chronic pancreatitis (ACP) and liver cirrhosis (ALC) are sequels of excessive alcohol intake. They develop in a minority of long-term alcohol consumers. Their concomitant occurrence is rare and the organ selection remains unknown. The aim of study was to compare patients with ACP and ALC with respect to their lifestyle. METHODS: Sixty-six patients with ACP and 80 with ALC were personally interviewed about their lifestyle, drinking, and eating habits. RESULTS: The groups of ACP (60 males, 6 females) and ALC (64 males, 16 females) did not differ in the amount of alcohol intake (58 g/day vs. 64 g/day). Significantly more patients with ACP reported first alcohol contact before the age of 15 (28.5% vs. 88%; p=0.03). ACP patients had the highest alcohol intake between 20 and 30 years of age (43.6% vs. 20.3%; p<0.01), were more likely to smoke (92.4% vs. 78.7%; p=0.02) and more likely to start smoking before the age of 15 (16.7% vs. 3.7%; p=0.04). Patients with ACP had a lower level of education (p<0.01). We did not observe significant differences between the dietary habits of the groups. The incidence of cirrhosis in ACP patients was 16.7%. The incidence of pancreatitis in the ACL group was 2.5%. CONCLUSION: The socio-behavioral factors affecting development of either ACP or ALC differed. ACP was associated with an early onset of drinking and smoking, highest alcohol intake at a young age, and a lower level of education. Simultaneous occurrence was unusual. Supported by grant IGAMZ NS/10527-3.

HDL and apolipoprotein A1 concentrations as markers of cholesterol efflux in middle-aged women: interaction with smoking.

OBJECTIVES: It has been demonstrated that the deleterious effect of smoking on the cardiovascular system is mediated through a decrease in protective HDL cholesterol. In addition, women are more sensitive to the negative effects of smoking, although the exact mechanism underlying this phenomenon is currently unknown. In this study, we evaluated whether smoking habits could modify the association of HDL cholesterol and apolipoprotein A1 (ApoA1) with reverse cholesterol transport (RCT), as measured by cholesterol efflux (CHE), in middle-aged women. DESIGN: The study group consisted of 39 healthy middle-aged women, 21 non-smokers (age 51.8±2.5 years, BMI 25.1±2.8 kg/m2) and 18 smokers (age 50.5±3.2 years, BMI 24.8±3.5 kg/m2). In addition to all traditional cardiovascular risk factors, CHE from macrophages, labelled during a 48-hour incubation in a medium containing [14C] cholesterol, to plasma acceptors in study subjects was established as a marker of reverse cholesterol transport. RESULTS: CHE was significantly higher in non-smokers than in smokers (14.22±1.75% vs. 13.17±1.33%; p<0.05). Smoking habit had no effect on the association of HDL with ApoA1 or HDL with CHE. However, in contrast to the strong association of ApoA1 with CHE in non-smokers (r=0.62; p<0.01), no such strong association was found in smokers (r=0.38; n.s.). Main findings and conclusion: Based on our results, smoking can alter ApoA1-mediated reverse cholesterol transport in women.

Which index best correlates with body fat mass: BAI, BMI, waist or WHR?

OBJECTIVES: The body mass index (BMI) has been the most commonly applied clinical measure to characterise body composition in individuals. However, the BMI has been criticised as being an inaccurate measure of body fatness. Recently, a new index reflecting body composition, the Body Adiposity Index (BAI) was proposed. The BAI was calculated using the equation BAI=((hip circumference)/ ((height)1.5) - 18). AIM: The aim of this study was to compare estimates of body fat content, i.e., body adiposity index (BAI), BMI, waist-hip ratio (WHR) and waist and hip circumferences, with respect to their ability to predict the percentage of body fat (PBF). RESULTS: To select an optimal surrogate for adiposity, we examined the correlation between body adiposity percentage as measured by BIA and several variables, including BAI, BMI and WHR. Correlations ranged from a high of 0.78 for BMI, 0.67 for BAI and 0.66 for waist circumference to a low value of 0.39 for the WHR index. The correlation between PBF and BAI (R=0.67, R2=0.45, p<0.001) and the correlation between PBF and BMI (R=0.78, R2=0.60, p<0.001) were of similar magnitude. CONCLUSION: Based on our results and those of other studies, we can say that the BAI index is not a universally valid index that could be used in the place of the BMI index in a Caucasian population; indeed, it would not accurately reflect body fat mass and thus could lead to an increased risk of obesity. Further, WHR index is not a suitable for an estimation of body fat.

Comparison of gene expression of epicardial and visceral adipocytes with regard to the differentiation stage.

BACKGROUND: Our study focused on the ability of epicardial adipocytes to produce bioactive substances and compare the extent of this production with the production of adipokines in visceral adipocytes, which are well known endocrine cells capable of contributing to the development of atherosclerosis. MATERIAL AND METHODS: The gene expression of human cytokines (IL-6, IL-8, IL-18, RANTES and MCP-1) and adipokines (leptin and adiponectin) was measured in primary cell lines of epicardial and visceral adipocytes, both in undifferentiated and mature statuses, after a 21-day-long differentiation protocol. Each condition was assayed in triplicate in two independent primary cell lines obtained from two different donors. RESULTS: The epicardial preadipocytes showed an increased expression of IL-8 (3.25-fold, p<0.05) compared with visceral preadipocytes. The expression of the atheroprotective adiponectin in epicardial preadipocytes was minimal compared with the expression in visceral preadipocytes (p<0.0001). Moreover, the expression of the genes of interest was dependent on the differentiation degree and cell origin. We observed an altered expression of the proinflammatory genes IL-8 (0.016-fold, p<0.01) and MCP-1 (0.19-fold, p<0.05) in differentiated epicardial adipocytes compared with undifferentiated adipocytes. The epicardial adipocytes showed an increased expression of IL-6 (8.13-fold, p<0.05) compared with the visceral adipocytes. CONCLUSION: Our results suggest that epicardial adipocytes substantially differ from visceral adipocytes and might locally contribute to the pathogenesis of coronary atherosclerosis.

The impact of left ventricle assist device on circulating endothelial microparticles - pilot study.

OBJECTIVES: Recent technological breakthroughs in the design of reliable systems for long term non-pulsatile mechanical heart support offer the possibility to study the effect of continuous blood flow in the vascular system. Generally, it is assumed that the absence of physiological pulsatile flow leads to prothrombogenic and proatherogenic changes. We investigated the change in the circulating endothelial microparticle concentration as a marker of endothelial damage in patients implanted with a continuous-flow left ventricle assist device (LVAD). METHODS: Endothelial microparticles were measured in 8 males (mean age 54.1±11.5 years) with terminal heart failure before and 3 months after implantation of an LVAD. The group consisted of 3 patients with dilated cardiomyopathy, 3 patients with ischemic cardiomyopathy, 1 patient with both conditions and 1 patient with congenital valvular disease. The concentration of endothelial microparticles was determined by ELISA Zymutest MP activity test. RESULTS: We did not observe a significant change in the concentration of circulating endothelial microparticles measured before and 3 months after implantation (p=0.669). High inter-individual variability in response to implantation was found. However, no association between a change in endothelial microparticle concentration and heart failure aetiology or a significant clinical complication attributed to LVAD implantation was observed. CONCLUSION: Results from this preliminary pilot study do not indicate that LVADs contribute to short-term vascular damage as defined by an increase in circulating endothelial microparticles.

SARS-CoV-2 vaccination in the context of original antigenic sin.

Immunological memory is the ability of the adaptive immune system to ensure a persistent protective effect after immunization. However, it can also be a limitation to building a sufficient level of protective antibodies specific to new mutations of the virus. It is imperative to bear this phenomenon (called "original antigenic sin") in mind and make every effort to overcome its inherent pitfalls when updating current and designing new vaccines.

Links between macrophages in perivascular adipose tissue and arterial wall: a role in atherosclerosis initiation?

BACKGROUND: Inflammation of adipose tissue in relation to atherosclerosis is currently widely studied in patients with advanced disease. However, data regarding polarization of adipose tissue and arterial wall macrophages and their mutual link in the early stages of atherosclerosis are scarce. The main aim of this cross-sectional study was to characterize macrophage subpopulations in arterial wall and adjacent adipose tissue; and to determine links between different subpopulations in a relatively healthy population living kidney donors. METHODS: The presence of cardiovascular risk factors was established in 68 living kidney donors. Macrophage polarization was analyzed by flow cytometry and confirmed by RT-PCR in samples of visceral adipose tissue, renal artery and adjacent perivascular adipose tissue collected during hand-assisted retroperitoneoscopic nephrectomy. RESULTS: CD14+CD16+CD36high macrophages were found only in adipose tissues and were strongly positively associated with several cardiovascular risk factors. The CD14+CD16+CD36low subpopulation was positively associated with the presence of several cardiovascular risk factors to a lesser extent in all studied tissues. In contrast, the proportion of CD14+CD16-CD36low macrophages was negatively linked to several cardiovascular risk factors and increased in subjects on statin therapy. The proportion of CD14+CD16+CD36low macrophages in perivascular, not visceral adipose tissue was associated with that of both macrophage subtypes in the arterial wall, suggesting a direct link between perivascular adipose tissue and the arterial wall. CONCLUSIONS: We confirmed the association of three macrophage subtypes in adipose tissue and arterial wall to the studied cardiovascular risk factors. Macrophage polarization in perivascular, but not visceral adipose tissue was linked to macrophage polarization in the arterial wall.

Rapid Drop in Coronary Heart Disease Mortality in Czech Male Population-What Was Actually behind It?

The high mortality of coronary heart disease (CHD) among Czech men-one of the highest worldwide-began to decline in 1991 soon after the abolition of government subsidies to all foodstuffs rich in animal fat. As participants in the WHO MONICA Project, we were able to analyze the CHD risk factors just before and after this major economic change. We had previously documented that the originally subsidized prices decreased animal fat consumption and consequently non-HDL cholesterol concentrations in the population. By the early 1990s, no progress had been made in the treatment of acute myocardial infarction, statins were unavailable as was not the currently more effective antihypertensive therapy. Our recent research proved a close relationship between cholesterolemia and proinflammatory macrophages in adipose tissue and accelerated macrophage polarization with increased palmitate and palmitoleate contents in cell membrane phospholipids. By contrast, the proportion of proinflammatory macrophages decreases with increasing presence of n-3 fatty acids in the cell membrane. The combination of non-HDL cholesterol drop and a decreased proportion of proinflammatory macrophages due to replacement of alimentary fat decreased CHD mortality immediately.

Effect of rosuvastatin treatment on cholesterol efflux from human macrophages.

OBJECTIVES: One of the positive effects of rosuvastatin is an increase in HDL cholesterol (HDL-C). An increase in HDL-C is considered as one of the positive effects of this type of statin, although it does not necessarily correspond to the actual reverse cholesterol transport (RCT) rate. We analyzed the influence of statin induced changes in HDL-C on cholesterol efflux (CHE), the key step affecting the RCT. DESIGN: Fourteen subjects (7 men, age: 50.9 ± 8.4 years and 7 women, age: 59.7 ± 10.6 years) with mixed dyslipidemia received 20 mg of rosuvastatin daily for 3 months. Before the initiation of statin therapy and at the end of the study period, the CHE from 14C cholesterol-labeled macrophages was determined in addition to parameters related to lipid metabolism. CHE was calculated as the percentage of radioactivity released from the macrophages into the media containing 5% of the examined plasma. RESULTS: The rosuvastatin administration resulted in significant reductions of total cholesterol, LDL cholesterol, and apolipoprotein B and a significant increase in HDL-C (from 1.43 mmol/l to 1.52 mmol/l, p=0.05), while the levels of apolipoprotein A1 remained unchanged. There was no significant increase in CHE (from 16.1% to 17.6%, p for trend = 0.053). Individual changes in HDL-C correlated significantly (p<0.05) with individual changes of CHE (r=0.76). CONCLUSION: Administration of rosuvastatin increases HDL-C, and individual changes correlate with the individual increases of CHE from macrophages.

Number of children is associated with plasma CRP levels.

BACKGROUND: C-reactive protein (CRP) is an acute-phase serum protein produced by the liver. High plasma levels of CRP have been associated primarily with infection, but elevated CRP levels have also been found to be associated with more than one hundred conditions and factors, including social and economic factors. MATERIALS AND METHODS: To evaluate the possible association between individuals' number of children and plasma levels of C-reactive protein, we studied a representative population of 2,426 adults. CRP was analyzed using the high sensitivity method (hsCRP). Individuals were divided into five groups of zero, one, two, three and four and more children. RESULTS: We found that individuals with more children had significantly higher levels of plasma hsCRP than individuals without children or than individuals with a low number of children (p for trend <0.001). This association could reflect the known associations between CRP and higher economic stress, exhaustion, episodic stress and chronic stress. CONCLUSIONS: We found significantly elevated levels of plasma CRP in individuals with more children than in individuals without children or with a low number of children.

An AHSG gene variant modulates basal metabolic rate and body composition development after a short-time lifestyle intervention.

OBJECTIVES: The AHSG (alpha2 Heremans-Schmid glycoprotein) gene is suggested to be important for the regulation of body fat and insulin sensitivity. Our study aimed to investigate the relationship between the common Thr248Met (rs4917) variant and obesity characteristics after an intervention with overweight females. MATERIAL AND METHODS: We analyzed 105 unrelated overweight/obese nondiabetic Czech adult females (49.0 ± 12.1 years, BMI over 28.6 kg/m2, mean BMI before intervention 32.8 ± 4.1 kg/m2) before and after 10 weeks of lifestyle modification. Biochemical and anthropometrical measurements were performed. The life style modification program consisted of a reduction of energy intake to an age-adjusted optimum and an exercise program (four units per week). The mean weight loss was 3.2 ± 3.5 kg (3.7 ± 4.0%). RESULTS: Thr/Thr homozygotes (N=52) increased lean muscle mass (p<0.05), decreased total body fat (kg) (p<0.005) and increased basal metabolic rate (BMR) per 1 kg body weight (p<0.005) in comparison with the Met carriers (N=52), but an association between BMI decrease and AHSG variants was not found. CONCLUSION: AHSG gene variants modify the effect of physical activity on BMR. Carriers of the Thr248Thr genotype showed a higher benefit from the lifestyle intervention (expressed as changes in body fat, active muscle and basal metabolic rate).

The consumption of the carp meat and plasma lipids in secondary prevention in the heart ischemic disease patients.

OBJECTIVES: Omega-3 fatty acids (FA) have been shown to be protective against cardiovascular diseases (CVD). The effect of the consumption of carp meat on CVD risk factors has not yet been examined in detail. We ascertained the influence of a diet enriched with carp meat with an elevated content of omega-3FA (200 g twice weekly for 4 weeks) in a group of subjects after cardiac revascularization surgery for ischemic heart disease with a follow-up spa treatment. DESIGN: After cardiac revascularization surgery, the probands consumed either a standard spa diet (56 individuals, 41 males, 15 females, age 41-80 years) or a diet enriched with two portions of carp meat (87 individuals, 64 males, 23 females, age 50-82 years). The differences in body mass index (kg/m²), blood pressure, plasma lipids and C-reactive protein (CRP) of the groups were analyzed. RESULTS: In the group with a higher consumption of carp meat, significantly greater improvements in lipid parameters in comparison to the standard spa diet were detected (total cholesterol p<0.001, triglycerides p<0.001, LDL-C p<0.001, CRP p<0.001, HDL-C p<0.001). No differences between these groups in blood pressure and body mass index were found. CONCLUSION: We conclude that the diet enriched with carp meat significantly improved plasma lipid parameters in patients after major cardiac revascularization surgery.

Post-infarction left ventricular free wall rupture: 12-years experience from the Cardiac Centre of the Institute of Clinical and Experimental Medicine in Prague, Czech Republic.

BACKGROUND: Post-infarction left ventricular free wall rupture (LVFWR) is a feared and catastrophic complication of myocardial infarction that carries a high surgical and hospital mortality. Due to the rarity of this complication, little information exists on surgical treatment and outcomes. Goal and Methods. The goal of this study was to present our experience with LVFWR. We present a retrospective cohort of 19 consecutive patients who were surgically treated in the Cardiac Centre of the Institute of Clinical and Experimental Medicine in Prague between January 2006 and December 2017. RESULTS: Thirty-day mortality was 26%. Five patients died. Four patients died in the operating theatre and one patient on the ninth postoperative day following re-rupture. Seventy-four percent of the patient cohort survived and were discharged from hospital. The median length of follow-up was 45 months (range 0.75-150). No patient died during follow-up. Median postoperative ejection fraction was 45% (range 25-65%). Angina pectoris and dyspnea were investigated during follow-up and graded according to the Canadian cardiology society (CCS) and the New York Heart Association (NYHA) classifications. Fourteen patients had CCS class I, eight patients had NYHA class I dyspnea and six patients had NYHA class II. Re-rupture occurred after hospital discharge in one patient one month after the original surgery. The patient was treated successfully by urgent surgical intervention. CONCLUSION: LVFWR is a catastrophic and challenging complication of myocardial infarction. Good outcomes can be achieved by rapid diagnosis and urgent surgical intervention as shown by our results.

Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation.

Statins represent one of the most widely used classes of drugs in current medicine. In addition to a substantial decrease in atherogenic low density lipoprotein (LDL) particle concentrations, several large trials have documented their potent anti-inflammatory activity. Based on our preliminary data, we showed that statins are able to decrease the proportion of pro-inflammatory macrophages (CD14+16+CD36high) in visceral adipose tissue in humans. In the present study including 118 healthy individuals (living kidney donors), a very close relationship between the pro-inflammatory macrophage proportion and LDL cholesterol levels was found. This was confirmed after adjustment for the most important risk factors. The effect of statins on the proportion of pro-inflammatory macrophages was also confirmed in an experimental model of the Prague hereditary hypercholesterolemia rat. A direct anti-inflammatory effect of fluvastatin on human macrophage polarization in vitro was documented. Based on modifying the LDL cholesterol concentrations, statins are suggested to decrease the cholesterol inflow through the lipid raft of macrophages in adipose tissue and hypercholesterolemia to enhance the pro-inflammatory macrophage phenotype polarization. On the contrary, due to their opposite effect, statins respond with anti-inflammatory activity, affecting the whole organism.