The Pathophysiology of HIV-/HAART-Related Metabolic Syndrome Leading to Cardiovascular Disorders: The Emerging Role of Adipokines

Individuals infected with human immunodeficiency virus (HIV) frequently demonstrate metabolic syndrome (MS) associated with increased incidence of cardiovascular disorders. Characteristics of HIV infection, such as immunodeficiency, viral load, and duration of the disease, in addition to the highly active antiretroviral therapy (HAART) have been suggested to induce MS in these patients. It is well documented that MS involves a number of traditional cardiovascular risk factors, like glucose, lipids, and arterial blood pressure abnormalities, leading to extensive atherogenic arterial wall changes. Nevertheless, the above traditional cardiovascular risk factors merely explain the exacerbated cardiovascular risk in MS. Nowadays, the adipose-tissue derivatives, known as adipokines, have been suggested to contribute to chronic inflammation and the MS-related cardiovascular disease. In view of a novel understanding on how adipokines affect the pathogenesis of HIV/HAART-related MS and cardiovascular complications, this paper focuses on the interaction of the metabolic pathways and the potential cardiovascular consequences. Based on the current literature, we suggest adipokines to have a role in the pathogenesis of the HIV/HAART-related MS. It is crucial to understand the pathophysiology of the HIV/HAART-related MS and apply therapeutic strategies in order to reduce cardiovascular risk in HIV patients

The Pathophysiology of HIV-/HAART-Related Metabolic Syndrome Leading to Cardiovascular Disorders: The Emerging Role of Adipokines. Exp Diabetes Res; 2012: 103063. Epub Dec. 8. Available at

Individuals infected with human immunodeficiency virus (HIV) frequently demonstrate metabolic syndrome (MS) associated with increased incidence of cardiovascular disorders. Characteristics of HIV infection, such as immunodeficiency, viral load, and duration of the disease, in addition to the highly active antiretroviral therapy (HAART) have been suggested to induce MS in these patients. It is well documented that MS involves a number of traditional cardiovascular risk factors, like glucose, lipids, and arterial blood pressure abnormalities, leading to extensive atherogenic arterial wall changes. Nevertheless, the above traditional cardiovascular risk factors merely explain the exacerbated cardiovascular risk in MS. Nowadays, the adipose-tissue derivatives, known as adipokines, have been suggested to contribute to chronic inflammation and the MS-related cardiovascular disease. In view of a novel understanding on how adipokines affect the pathogenesis of HIV/HAART-related MS and cardiovascular complications, this paper focuses on the interaction of the metabolic pathways and the potential cardiovascular consequences. Based on the current literature, we suggest adipokines to have a role in the pathogenesis of the HIV/HAART-related MS. It is crucial to understand the pathophysiology of the HIV/HAART-related MS and apply therapeutic strategies in order to reduce cardiovascular risk in HIV patients

An update on markers of carotid atherosclerosis in patients with Type 2 diabetes

Carotid atherosclerosis constitutes an important cause of ischemic brain attack and stroke, accounting for up to 40% of cases of ischemic cerebrovascular disease. Type 2 diabetes mellitus is an independent risk factor for stroke and its recurrence. Thus, identifying diabetic patients who are at high risk of developing stroke is of great clinical importance. Noninvasive measurements of surrogate markers of atherosclerosis, such as novel serum biomarkers, can be helpful in detecting subclinical carotid disease, especially among individuals at the highest cardio-/cerebro-vascular risk. Previous studies have proposed an expanding body of serum biomarkers, such as C-reactive protein, fibrinogen, adipokines, cytokines and growth factors, as novel indicators of carotid atherosclerosis development that predict carotid-related clinical outcomes. Furthermore, those biomarkers are expected to assess the efficacy of both pharmaceutical and interventional strategies. Accordingly, it is increasingly clear that measuring biomarkers may improve the definition of cerebrovascular risk profile in patients with Type 2 diabetes mellitus

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block

Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases

The role of exercise training and the endocannabinoid system in atherosclerotic plaque burden and composition in Apo-E-deficient mice

Introduction: We investigated the effect of combining exercise training and treatment with an endocannabinoid receptor 1 inhibitor (Rimonabant) on atherosclerosis burden and composition. Methods: Forty-eight apolipoprotein E-deficient (ApoE-/-) mice were kept on a 16-week high-fat diet. Mice were then placed on a normal diet and were randomized to the following groups with n=12 mice for 6 more weeks: 1) Control (Co) - no intervention; 2) Exercise (Ex) - exercise training on treadmill; 3) Rimonabant (Ri) - oral administration of rimonabant (10 mg/kg/day); or 4) Rimonabant+Exercise (RiEx) - combination of Ri and Ex groups treatment. At the end, all animals were sacrificed, and blood samples, as well as aortic root specimens, were obtained for histomorphometric analysis and quantification of the serum and plaque content of matrix metalloproteinases (MMPs). Results: The mean plaque area was significantly smaller (RiEx: 43.18±1.72%, Ri: 44.66±3.1%, Ex: 49±4.10%, Co: 70.43±2.83%) in all active treatment groups relative to the Co group (p<0.01). Conversely, the relative concentrations of collagen and elastin were increased significantly across all treatment groups compared to Co (p<0.05). Immunohistochemical analysis revealed significantly reduced macrophage content within plaques after all interventions, with the most pronounced effect observed after combined treatment (RiEx: 9.4±3.92%, Ri: 15±2.45%, Ex: 19.78±2.79%, Co: 34.25±4.99%; p<0.05). Within plaques, the TIMP-1 concentration was significantly upregulated in exercise-treated groups. MMP-3 and MMP-9 concentrations were equivalently decreased in all three active treatment groups compared to controls (p<0.001). Discussion: Both exercise and rimonabant treatments induced plaque regression and promoted plaque stability. The combined treatment failed to show additive or synergistic benefits relative to either intervention alone