Naga Venkata Pothineni

Inflammation and atherosclerosis--revisited.

Atherogenesis has been traditionally viewed as a metabolic disease representing arterial obstruction by fatty deposits in its wall. Today, it is believed that atherogenesis involves highly specific biochemical and molecular responses with constant interactions between various cellular players. Despite the presence of inflammatory reaction in each and every step of atherosclerosis from its inception to terminal manifestation, the cause–effect relationship of these 2 processes remains unclear. In this article, we have attempted to review the role of inflammation in the development of atherosclerosis and in its major complication—coronary heart disease.

Metabolic Syndrome: Does it Differ Between Women and Men?

Cardiovascular disease represents a massive healthcare burden worldwide. Gender differences in the pathophysiology, presentation and prognosis of cardiovascular disease have been described in the literature. Metabolic syndrome, characterized by a cluster of metabolic abnormalities is associated with increased risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. With the global obesity epidemic, the prevalence of metabolic syndrome is rising rapidly in the developed as well as developing world. However, there is considerable variation in the prevalence based on geography, age, sex and, definition used for diagnosis. Data on gender related differences in metabolic syndrome is relatively scarce. Here, we aim to review the gender differences in epidemiology and pathophysiology of metabolic syndrome as well as its individual components. Knowledge of gender differences in metabolic syndrome can help design gender specific preventative and therapeutic strategies that will have a positive impact on overall population health.

Impact of Hepatitis C Seropositivity on the Risk of Coronary Heart Disease Events

Chronic infections have been shown to enhance atherogenicity. However, the association between chronic hepatitis C (HCV) and coronary heart disease (CHD) remains controversial. We examined the risk for CHD events in patients with HCV with an emphasis on the risk of CHD events with active infection. We conducted a retrospective cohort study using the Enterprise Data Warehouse at the University of Arkansas for Medical Sciences. HCV positive and negative patients were identified based on serology and incident CHD events were studied. Patient characteristics at entry were compared either by analysis of variance/F-test (continuous variables) or by a Chi-squared test (categorical variables). The joint effect of risk factors for incident CHD was evaluated using logistic regression. A total of 8,251 HCV antibody positive, 1,434 HCV RNA positive and 14,799 HCV negative patients were identified. HCV antibody and RNA positive patients had a higher incidence of hypertension, diabetes mellitus, obesity and chronic lung disease, but lower serum cholesterol levels compared to HCV negative patients (p< 0.001). HCV seropositive patients had a higher incidence of CHD events when compared to controls (4.9% vs. 3.2%, p<0.001). In the HCV cohort, patients with detectable HCV RNA had a significantly higher incidence of CHD events when compared to patients who were only HCV antibody positive with no detectable RNA (5.9% vs. 4.7%, p=0.04). In multivariate logistic regression analysis, both HCV antibody positivity (OR 1.32, 95% CI 1.09-1.60, p<0.001) and HCV RNA positivity (OR 1.59, 95% CI 1.13-2.26, p<0.001) were independent risk factors for incident CHD events. In conclusion, there is increased incidence of CHD events in HCV seropositive patients and the incidence is much higher in patients with detectable HCV RNA when compared to patients with remote infection who are only antibody positive. Lipid profile does not appear to be a good cardiovascular risk stratification tool in HVC patients.

LOX-1, a bridge between GLP-1R and mitochondrial ROS generation in human vascular smooth muscle cells.

A growing body of evidence indicates that glucagon-like peptide-1 (GLP-1) agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors play an important role in modulating oxidant stress in vascular beds. However, the underlying mechanism of this process remains unclear. In recent studies, we observed an increase in GLP-1 receptor (GLP-1R) expression in the aorta of LOX-1 knock-out mice. Since LOX-1 is a pivotal regulator of reactive oxygen species (ROS), we conducted studies to identify relationship between LOX-1, ROS and GLP-1 agonism or DPP-4 antagonism. We observed a sustained decrease in GLP-1R expression in human vascular smooth muscle cells (VSMCs) treated with ox-LDL. When VSMCs were treated with different concentration of liraglutide (a GLP-1 agonist) or NVPDPP728 (a DPP-4 inhibitor), expression of ROS decreased compared with ox-LDL alone treatment. To further prove that LOX-1 plays a pivotal role in ROS and GLP-1R expression, we treated VSMCs with LOX-1 antibody or transfected cells with human LOX-1 cDNA. The inhibitory effect of ox-LDL on GLP-1R expression was reversed with anti-LOX-1 antibody treatment, while the inhibitory effect of liraglutide and NVPDPP728 on ROS generation was attenuated when cells were transfected with LOX-1 cDNA. Our results suggest that LOX-1 may play a bridging role in GLP-1 activation and ROS interaction.

Oxidative Stress in Atherosclerosis

Purpose of ReviewAtherosclerosis is now considered a chronic inflammatory disease. Oxidative stress induced by generation of excess reactive oxygen species has emerged as a critical, final common mechanism in atherosclerosis. Reactive oxygen species (ROS) are a group of small reactive molecules that play critical roles in the regulation of various cell functions and biological processes. Although essential for vascular homeostasis, uncontrolled production of ROS is implicated in vascular injury. Endogenous anti-oxidants function as checkpoints to avoid these untoward consequences of ROS, and an imbalance in the oxidant/anti-oxidant mechanisms leads to a state of oxidative stress. In this review, we discuss the role of ROS and anti-oxidant mechanisms in the development and progression of atherosclerosis, the role of oxidized low-density lipoprotein cholesterol, and highlight potential anti-oxidant therapeutic strategies relevant to atherosclerosis.Recent FindingsThere is growing evidence on how traditional risk factors translate into oxidative stress and contribute to atherosclerosis. Clinical trials evaluating anti-oxidant supplements had failed to improve atherosclerosis. Current studies focus on newer ROS scavengers that specifically target mitochondrial ROS, newer nanotechnology-based drug delivery systems, gene therapies, and anti-miRNAs. Synthetic LOX-1 modulators that inhibit the effects of Ox-LDL are currently in development.SummaryResearch over the past few decades has led to identification of multiple ROS generating systems that could potentially be modulated in atherosclerosis. Therapeutic approaches currently being used for atheroslcerotic vascular disease such as aspirin, statins, and renin-angiotensin system inhibitors exert a pleiotropic antioxidative effects. There is ongoing research to identify novel therapeutic modalities to selectively target oxidative stress in atherosclerosis.

U.S. Trends in Inpatient Utilization of Fractional Flow Reserve and Percutaneous Coronary Intervention.

Fractional flow reserve (FFR) of intermediate coronary stenosis is a highly accurate, reproducible, and cost-effective modality with powerful prognostic value. Results of the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) [(1)][1] and FAME-2 trials [(2)][2] have shown a

Complication rates of atrial fibrillation ablations: Comparison of safety outcomes from real world to contemporary randomized control trials

outcomes from real world to contemporary randomized control trials☆ Naga Venkata K. Pothineni , Abhishek Deshmukh ⁎, Sadip Pant , Nileshkumar J. Patel , Apurva Badheka , Ankit Chothani , Neeraj Shah , KathanMehta , Ghanshyambhai T. Savani , Vikas Singh , Peeyush Grover , Vipulkumar Bhalara , Nilay Patel , Shilpkumar Arora , Ankit Rathod , Juan Viles-Gonzalez , Hakan Paydak a a University of Arkansas, Little Rock, AR, United States b Staten Island University Hospital, Staten Island, NY, United States c Detroit Medical Center, Detroit, MI, United States d MedStar Washington Hospital Center, Washington, DC, United States e UPMC Shadyside Hospital, Pittsburgh, PA, United States f University of Miami Miller School of Medicine, Miami, FL, United States g Cedar-Sinai Medical Center, Los Angeles, CA, United States

Infections, atherosclerosis, and coronary heart disease

Atherosclerosis is a chronic inflammatory disease. Pathophysiological similarities between chronic infections and atherosclerosis triggered interest in a clinical association between these conditions. Various infectious microbes have been linked to atherosclerotic vascular disease in epidemiological studies. However, this association failed to satisfy the Kochs postulates of causation with multiple clinical trials demonstrating inefficacy of anti-infective therapies in mitigating atherosclerotic cardiovascular events. Identification of underlying pathophysiological mechanisms and experience with vaccination against various infectious agents has ushered a new avenue of efforts in the development of an anti-atherosclerotic vaccine. Studies in animal models have identified various innate and adaptive immune pathways in atherosclerosis. In this review, we discuss the patho-biological link between chronic infections and atherosclerosis, evaluate existing evidence of animal and human trials on the association between infections and cardiovascular disease and introduce the concept of an anti-atherosclerotic vaccine.

Gender Differences in Autonomic Control of the Cardiovascular System

BACKGROUND The autonomic nervous system (ANS) is a key regulator of the cardiovascular system. The two arms of the ANS, sympathetic and parasympathetic (vagal) have co-regulatory effects on cardiac homeostasis. ANS modulation and dysfunction are also believed to affect various cardiac disease states. Over the past decade, there has been increasing evidence suggesting gender differences in ANS activity. METHODS In multiple previous studies, ANS activity was primarily assessed using heart rate variability, muscle sympathetic nerve activity, coronary blood flow velocity, and plasma biomarkers. Heart rate variability is a non-invasive measure, which can be analyzed in terms of low frequency and high frequency oscillations, which indicate the sympathetic and parasympathetic tone, respectively. These measures have been studied between women and men in states of rest and stress, and in cardiac disease. CONCLUSION Studies support the concept of a significant gender difference in ANS activity. Further studies are indicated to elucidate specific differences and mechanisms, which could guide targeted therapy of various cardiovascular disease states.

Metabolic syndrome: pathophysiology, management, and modulation by natural compounds:

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that include hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia, and is strongly associated with an increased risk for developing diabetes and atherosclerotic and nonatherosclerotic cardiovascular disease (CVD). The pathogenesis of MetS involves both genetic and acquired factors that contribute to the final pathway of inflammation that leads to CVD. MetS has gained significant importance recently due to the exponential increase in obesity worldwide. Early diagnosis is important in order to employ lifestyle and risk factor modification. Here, we review the epidemiology and pathogenesis of MetS, the role of inflammation in MetS, and summarize existing natural therapies for MetS.