B cells and atherosclerosis: A HIV perspective.

Atherosclerosis remains a leading cause of cardiovascular disease (CVD) globally, with the complex interplay of inflammation and lipid metabolism at its core. Recent evidence suggests a role of B cells in the pathogenesis of atherosclerosis; however, this relationship remains poorly understood, particularly in the context of HIV. We review the multifaceted functions of B cells in atherosclerosis, with a specific focus on HIV. Unique to atherosclerosis is the pivotal role of natural antibodies, particularly those targeting oxidized epitopes abundant in modified lipoproteins and cellular debris. B cells can exert control over cellular immune responses within atherosclerotic arteries through antigen presentation, chemokine production, cytokine production, and cell-cell interactions, actively participating in local and systemic immune responses. We explore how HIV, characterized by chronic immune activation and dysregulation, influences B cells in the context of atherosclerosis, potentially exacerbating CVD risk in persons with HIV. By examining the proatherogenic and antiatherogenic properties of B cells, we aim to deepen our understanding of how B cells influence atherosclerotic plaque development, especially within the framework of HIV. This research provides a foundation for novel B cell-targeted interventions, with the potential to mitigate inflammation-driven cardiovascular events, offering new perspectives on CVD risk management in PLWH.

Virus-Associated CD8+ T-Cells Are Not Activated Through Antigen-Mediated Interaction Inside Atherosclerotic Lesions.

INTRODUCTION: Viral infections have been associated with the progression of atherosclerosis and CD8+ T-cells directed against common viruses, such as influenza, Epstein-Barr virus, and cytomegalovirus, have been detected inside human atherosclerotic lesions. These virus-specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis; however, whether they affect disease progression directly remains unclear. In this study, we aimed to characterize the activation status of virus-specific CD8+ T-cells in the atherosclerotic lesion. METHODS: The presence, clonality, tissue enrichment, and phenotype of virus-associated CD8+ T-cells in atherosclerotic lesions were assessed by exploiting bulk T-cell receptor-ß sequencing and single-cell T-cell receptor (α and ß) sequencing datasets on human endarterectomy samples and patient-matched blood samples. To investigate if virus-specific CD8+ T-cells can be activated through T-cell receptor stimulation in the atherosclerotic lesion, the immunopeptidome of human plaques was determined. RESULTS: Virus-associated CD8+ T-cells accumulated more in the atherosclerotic lesion (mean=2.0%), compared with patient-matched blood samples (mean=1.4%; P=0.05), and were more clonally expanded and tissue enriched in the atherosclerotic lesion in comparison with nonassociated CD8+ T-cells from the lesion. Single-cell T-cell receptor sequencing and flow cytometry revealed that these virus-associated CD8+ T-cells were phenotypically highly similar to other CD8+ T-cells in the lesion and that both exhibited a more activated phenotype compared with circulating T-cells. Interestingly, virus-associated CD8+ T-cells are unlikely to be activated through antigen-specific interactions in the atherosclerotic lesion, as no virus-derived peptides were detected on HLA-I in the lesion. CONCLUSIONS: This study suggests that virus-specific CD8+ T-cells are tissue enriched in atherosclerotic lesions; however, their potential contribution to inflammation may involve antigen-independent mechanisms.

Subclinical atherosclerosis and immune activation in young HIV-infected patients with telomere shortening.

BACKGROUND: To date, available data on premature aging in young HIV-infected adults are scarce and no reports offer comprehensive assessment of telomere shortening (TS) in relation to subclinical atherosclerosis (SCA). In this study, we investigate if telomere shortening and immune activation markers are associated with SCA, which is one of the main degenerative diseases in young HIV-infected adults. METHODS: A descriptive cross-sectional study was carried out in 149 HIV-infected patients on stable antiretroviral regimen (ART). Carotid intima-media thickness (cIMT) was estimated by carotid ultrasound. Quantitative singleplex PCR was performed to evaluate TS. The expression of activation/senescence markers was evaluated by multiparametric flow cytometry. RESULTS: TS was observed in 73 patients (49%). Higher cIMT was observed in patients with TS than those without it (0.86 vs. 0.80 mm; p=0.041). Patients under the age of 50 (defined as young adults) with TS showed higher absolute numbers of activated lymphocyte T cells CD8+CD38+ (3.94 vs. 2.34 cell/µl; p=0.07) and lymphocyte B cells CD19+CD38+ (3.07 vs. 2.10 cell/µl; p=0.004) compared to those without TS. In the multivariate analysis, the only factor independently associated with TS was the absolute number of lymphocyte T cells CD8+CD38+ T cells (OR = 1.18; 95%-CI = 1.00-1.39; p = 0.05). CONCLUSION: Young HIV-infected adults show premature biological aging with accentuated immune activation. Chronic inflammation with excessive T-cells activation could be associated to TS, premature aging, and SCA in young HIV-infected adults.

Extracellular Vesicles: Versatile Nanomediators, Potential Biomarkers and Therapeutic Agents in Atherosclerosis and COVID-19-Related Thrombosis.

Cells convey information among one another. One instrument employed to transmit data and constituents to specific (target) cells is extracellular vesicles (EVs). They originate from a variety of cells (endothelial, immune cells, platelets, mesenchymal stromal cells, etc.), and consequently, their surface characteristics and cargo vary according to the paternal cell. The cargo could be DNA, mRNA, microRNA, receptors, metabolites, cytoplasmic proteins, or pathological molecules, as a function of which EVs exert different effects upon endocytosis in recipient cells. Recently, EVs have become important participants in a variety of pathologies, including atherogenesis and coronavirus disease 2019 (COVID-19)-associated thrombosis. Herein, we summarize recent advances and some of our own results on the role of EVs in atherosclerotic cardiovascular diseases, and discuss their potential to function as signaling mediators, biomarkers and therapeutic agents. Since COVID-19 patients have a high rate of thrombotic events, a special section of the review is dedicated to the mechanism of thrombosis and the possible therapeutic potential of EVs in COVID-19-related thrombosis. Yet, EV mechanisms and their role in the transfer of information between cells in normal and pathological conditions remain to be explored.

The impact of atherosclerotic cardiovascular disease, dyslipidaemia and lipid lowering therapy on Coronavirus disease 2019 outcomes: an examination of the available evidence.

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.

Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells.

Human Cytomegalovirus (CMV) infection is associated with atherosclerosis, higher cardiovascular disease (CVD) risk, and an increase in memory T-cells (Tmem). T-cells have also been implicated in CVD, independently of CMV infection. To better understand the CMV-associated CVD risk, we examined the association between CMV (IgG) serostatus and central aortic (carotid-to-femoral) pulse wave velocity (cfPWV), an early, independent predictor of CVD. We also investigated if such an association might be reflected by the distribution of Tmem and/or other T-cell subsets. Methods: Healthy older volunteers (60-93 years) underwent routine clinical and laboratory evaluation, including assessment of cfPWV in eligible participants. Flow-cytometry was used to assess proportions of memory T-cells, CD28null T-cells, and CMV-specific T-cells. The following associations were examined; CMV serostatus/cfPWV, CMV serostatus/proportion of Tmem, proportion of Tmem/cfPWV, CD28null T-cells/cfPWV, and CMV-specific T-cells/cfPWV. Linear regression models were used to adjust for age, sex, socioeconomic status, smoking, waist-to-hip ratio, cholesterol, and blood pressure as required. Results: Statistically significant positive associations were found (P-values for the fully adjusted models are given); CMV serostatus/cfPWV in men (P ≤ 0.01) but not in women, CMV serostatus/proportions of CD4 Tmem in men (P ≤ 0.05) but not in women; proportions of CD4 Tmem/cfPWV among CMV seropositive (CMV+) people (P ≤ 0.05) but not CMV seronegative (CMV-) people. Conclusion: CMV infection increases the CVD risk of older men by increasing cfPWV. This may be mediated in part by increased proportions of CD4 Tmem, higher numbers of which are found in CMV+ older people and more so among men than women. Given the high prevalence of CMV worldwide, our findings point to a significant global health issue. Novel strategies to mitigate the increased CVD risk associated with CMV may be required.

Potential mechanisms of cerebrovascular diseases in COVID-19 patients.

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.

Increased frequency of HLA-A*02 in patients with atherosclerosis is associated with VZV seropositivity.

BACKGROUND: HLA molecules are inherited key molecules in the immune inflammation and specific responses to environmental pathogens. We investigated the association of HLA-A alleles with Varicella zoster virus (VZV) seropositivity in patients with atherosclerosis (AS). MATERIALS AND METHODS: Plasma Anti-VZV IgG and molecular HLA type were detected in 203 (100 AS+ and 103 AS-) individuals. RESULTS: Of 100 AS+ individuals, 66 were anti-VZV+ and 34 were anti-VZV-. Of 103 age/sex-matched AS- individuals, 59 were anti-VZV+ and 44 were anti-VZV-. Anti-VZV-IgG in AS+ cases was higher than AS- controls (p = .034). The mean anti-VZV IgG in HLA-A*02+AS+ individuals was higher than HLA-A*02+AS- controls (p < .001). HLA-A*02 was associated with VZV-seropositivity (p = .01) in AS+ patients. A higher frequency of HLA-A*02-allele in AS+ patients compared to AS- controls (p = .015) and an accumulation of HLA-A*02-allele in AS+ anti-VZV+ group (33.3%, p = .004) was observed. CONCLUSIONS: HLA-A alleles and immune responses to VZV are associated with clinical atherosclerosis.

Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study.

OBJECTIVE: To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. METHODS: We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/µL, not starting c-ART; and group B, CD4<500 cells/µL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. RESULTS: The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. CONCLUSIONS: In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.

The role of human cytomegalovirus in atherosclerosis: a systematic review.

Atherosclerosis is a progressive vascular disease with increasing morbidity and mortality year by year in modern society. Human cytomegalovirus (HCMV) infection is closely associated with the development of atherosclerosis. HCMV infection may accelerate graft atherosclerosis and the development of transplant vasculopathy in organ transplantation. However, our current understanding of HCMV-associated atherosclerosis remains limited and is mainly based on clinical observations. The underlying mechanism of the involvement of HCMV infection in atherogenesis remains unclear. Here, we summarized current knowledge regarding the multiple influences of HCMV on a diverse range of infected cells, including vascular endothelial cells, vascular smooth muscle cells, monocytes, macrophages, and T cells. In addition, we described potential HCMV-induced molecular mechanisms, such as oxidative stress, endoplasmic reticulum stress, autophagy, lipid metabolism, and miRNA regulation, which are involved in the development of HCMV-associated atherogenesis. Gaining an improved understanding of these mechanisms will facilitate the development of novel and effective therapeutic strategies for the treatment of HCMV-related cardiovascular disease.

Infection and atherosclerosis: TLR-dependent pathways.

Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.

Age-specific associations between HIV infection and carotid artery intima-media thickness in China: a cross-sectional evaluation of baseline data from the CHART cohort.

BACKGROUND: Inconclusive results have been reported in studies evaluating the association between HIV infection and subclinical atherosclerosis. Unsolved issues include whether the increased atherosclerosis burden observed in some studies is attributed to greater prevalence of traditional risk factors or HIV infection. Therefore, we evaluated the association of HIV infection with subclinical atherosclerosis as assessed by carotid artery intima-media thickness, while controlling for the effects of traditional risk factors as operationalised by the Framingham risk score (FRS). METHODS: We did a cross-sectional evaluation of data derived from the baseline assessment of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, an ongoing longitudinal study being done in Zhejiang province, China. HIV-positive and HIV-negative individuals aged 18 years and older were recruited between Feb 1, and Dec 10, 2017, and were frequency-matched for age and sex in a 1:2 ratio. Subclinical atherosclerosis was defined as carotid artery intima-media thickness of 780 µm or higher. Logistic regression was used to assess the associations of HIV-positive serostatus and FRS with subclinical atherosclerosis. FINDINGS: 480 of 1425 (36·1%, 95% CI 33·6-38·6) HIV-positive and 784 of 2850 (27·5%, 95% CI 25·9-29·2) HIV-negative individuals had subclinical atherosclerosis (p<0·0001), and these patterns remained significant (adjusted odds ratio [adjOR] 1·72, 95% CI 1·47-2·01) in the adjusted model. After stratifying by age, higher prevalence of subclinical atherosclerosis was observed in HIV-positive than in HIV-negative individuals across the age groups 18-29 years (41 [16·0%] of 256 vs 13 [2·5%] of 512, p<0·0001), 30-44 years (128 [24·0%] of 533 vs 153 [14·4%] of 1066, p<0·0001), and 45-59 years (182 [46·6%] of 391 vs 294 [37·6%] of 782, p=0·0032), but not 60-75 years (163 [66·5%] of 245 vs 324 [66·1%] of 490, p=0·912). Significant negative interaction between HIV-positive serostatus and age on subclinical atherosclerosis was observed (p<0·0001). ORs adjusted for age, sex, and FRS were 8·84 (95% CI 4·50-17·34) for the age group 18-29 years, 2·09 (1·59-2·74) for 30-44 years, 1·54 (1·19-1·98) for 45-59 years, and 1·04 (0·75-1·44) for 60-75 years. Among HIV-positive individuals, none of the HIV-specific variables were significantly associated with carotid artery intima-media thickness estimates except for being antiretroviral therapy naive. INTERPRETATION: HIV infection is associated with subclinical atherosclerosis, independent of classic risk factors. The association is stronger at younger ages, suggesting early onset of subclinical atherosclerosis among young adults. These findings highlight the need to modify HIV/AIDS treatment guidelines to incorporate cardiovascular evaluation in China. FUNDING: China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, and Shanghai Municipal Health and Family Planning Commission.

Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study.

BACKGROUND: More than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857. FINDINGS: Our search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18-1·39). Globally, 1·5 million (95% CI 0·9-2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs. INTERPRETATION: HCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries. FUNDING: British Heart Foundation and Wellcome Trust.

Prevalence of Subclinical Atherosclerosis and Risk of Atherosclerotic Cardiovascular Disease in Older Adults Living with HIV.

Cardiovascular disease (CVD) is one among the leading causes of mortality in people living with HIV on antiretroviral treatment (ART) worldwide. We examined the prevalence of subclinical atherosclerosis, associated factors, and risk of CVD in older adults living with HIV (OALHIV). A cross-sectional study was conducted with patients aged ≥50 years with HIV infection receiving ART at community hospitals in Chiang Mai, Thailand. Age- and sex-matched patients without documented HIV infection who visited the general outpatient department were enrolled for comparison. Cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) were measured using the vascular screening system, VaSera System™ (Fukuda Denshi Co., Ltd., Japan) to determine subclinical atherosclerosis (defined as CAVI ≥9.0) and peripheral arterial disease (defined as ABI <0.9), respectively. The Ramathibodi-Electric Generating Authority of Thailand (RAMA-EGAT) scores to predict the risk of coronary stenosis and the 10-year risk of ASCVD by pooled cohort equation were calculated. One hundred fifty-five patients were enrolled (107 HIV/48 comparison). The mean age was 59.0 years (SD 6.1); 67 (43%) were male. Participants in the HIV and comparison group were similar with respect to abnormal CAVI (57% vs. 58%, p = .88), abnormal ABI (6% vs. 8%, p = .50), and the risk of coronary stenosis (34% vs. 44%, p = .23). However, the 10-year risk of ASCVD was lower in HIV than in the comparison group (29% vs. 48%, p = .02). In OALHIV, diabetes mellitus was the only factor associated with abnormal CAVI. The cardiovascular risk among OALHIV in this study was similar to non-HIV population. More than a half of them had abnormal CAVI, and approximately one-third was at ≥10% 10-year risk of ASCVD.

HTLV-1-host interactions facilitate the manifestations of cardiovascular disease.

Atherosclerosis is a multifactorial life-threatening disease which an epidemiologic study in Northeastern Iran showed its association with HTLV-1 infection. Therefore, a cross-sectional study of 39 newly diagnosed subjects with angiography test in three groups including 14 coronary artery disease+HTLV-1+ (CAD+HTLV-1+), 8 CAD-HTLV-1+, and 17 CAD+HTLV-1- patients and 11 healthy subjects (CAD-HTLV-1-) were conducted. In the present study, Tax and proviral load (PVL) as HTLV-1 virulence factors, along with host chemokine receptor 1 (CCR1), and CCR2 were investigated. Real-time PCR TaqMan method was carried out for PVL measurement and HTLV-1-Tax, CCR1, and CCR2 expressions in peripheral blood mononuclear cells (PBMCs). Furthermore, the main risk factors, lipid profile, and complete blood count (CBC) were assessed. Expression of CCR1 in CAD+HTLV-1+ group was higher than CAD-HTLV-1+ (P = 0.01) and healthy subjects (P = 0.02). Expression of CCR1 in CAD+HTLV-1+ was higher in comparison with CAD+HTLV-1-group but did not meet 95% CI (P = 0.02), but meaningful at 91% CI. In addition, expression of CCR2 in CAD+HTLV-1+ subjects was higher than CAD-HTLV-1+ and CAD+HTLV-1- (P = 0.001, P = 0.005, respectively). In CAD+HTLV-1- subjects, CCR2 was higher than CAD-HTLV-1+ (P = 0.03). The mean PVL in CAD+HTLV-1+ group is more than CAD-HTLV-1+ (P = 0.041). In HTLV-1+ patients Tax had a positive correlation with cholesterol (R = 0.59, P = 0.01), LDL (R = 0.79, P = 0.004) and a negative correlation with HDL (R = -0.47, P = 0.04). These correlations were stronger in CAD+HTLV-1+. Findings showed that HTLV-1 could alter the expression of CCR2 and, less effect, on CCR1. Moreover, the strong correlation between CCR2 and HTLV-1-Tax with cholesterol, LDL and HDL showed that Tax as the main HTLV-1 virulence factor in cytokine deregulation might be had indirect effects on cholesterol, LDL, and HDL levels.

Influenza virus and atherosclerosis.

Influenza viruses infect the upper respiratory system, causing usually a self-limited disease with mild respiratory symptoms. Acute lung injury, pulmonary microvascular leakage and cardiovascular collapse may occur in severe cases, usually in the elderly or in immunocompromised patients. Acute lung injury is a syndrome associated with pulmonary oedema, hypoxaemia and respiratory failure. Influenza virus primarily binds to the epithelium, interfering with the epithelial sodium channel function. However, the main clinical devastating effects are caused by endothelial dysfunction, thought to be the main mechanism leading to pulmonary oedema, respiratory failure and cardiovascular collapse. A significant association was found between influenza infection and acute myocardial infarction (AMI). The incidence of admission due to AMI during an acute viral infection was six times as high during the 7 days after laboratory confirmation of influenza infection as during the control interval (10-fold in influenza B, 5-fold in influenza A, 3.5-fold in respiratory syncytial virus and 2.7-fold for all other viruses). Our review will focus on the mechanisms responsible for endothelial dysfunction during influenza infection leading to cardiovascular collapse and death.