A S Antonopoulos

Reciprocal Effects of Systemic Inflammation and Brain Natriuretic Peptide on Adiponectin Biosynthesis in Adipose Tissue of Patients With Ischemic Heart Disease

Objective— To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease. Approach and Results— In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-&agr;, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged. Conclusions— This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.

Interrelationship between diabetes mellitus and heart failure: the role of peroxisome proliferator-activated receptors in left ventricle performance

Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction. On the other hand, when HF exists, hypoperfusion of the liver and pancreas, b-blocker and diuretic treatment, and autonomic nervous system dysfunction may cause impairment of glucose metabolism. These molecular pathways may be used as therapeutic targets for novel antidiabetic agents. Peroxisome proliferator-activated receptors (PPARs) not only improve insulin resistance and glucose and lipid metabolism but also manifest a diversity of actions directly or indirectly associated with systolic or diastolic performance of left ventricle and symptoms of HF. Interestingly, they may beneficially affect remodeling of the left ventricle, fibrosis, and diastolic performance but they may cause impaired water handing, sodium retention, and decompensation of HF which should be taken into consideration in the management of patients with DM. In this review article, we present the pathophysiological data linking HF with DM and we focus on the molecular mechanisms of PPARs agonists in left ventricle systolic and diastolic performance providing useful insights in the molecular mechanism of this class of metabolically active regiments.

Coronary versus carotid artery plaques. Similarities and differences regarding biomarkers morphology and prognosis

HIGHLIGHTSCarotid and coronary artery disease are two major artherosclerotic conditions.Atherosclerotic plaque development in both locations share similar characteristics.However differences exist regarding risk factors, plaque biology and progression.These differences dictate the different use of diagnostic modalities and treatment goals. &NA; Carotid and coronary artery disease are two major atherosclerotic conditions that have shown an increased prevalence in the last three decades that is associated with high morbidity and mortality. Recent data have revealed that the development of the atherosclerotic plaque — the basic entity in both diseases — may share similar characteristics and mechanisms irrespective of the location site. Even though the biology of atherosclerotic process is similar, there are differences in plaque morphology and characteristics. Indeed, plaque erosion, calcified nodules, fibrous cap thickness and macrophage accumulation may be different in the setting of coronary and carotid artery disease. The perivascular adipose tissue surrounding the coronary arteries (but not carotids) could also affect plaque biology. In this review we focus on comparative the characteristics of both types of atherosclerotic plaques and summarize existing knowledge to provide useful conclusions about current and future treatment strategies.

Prognostic significance of arterial stiffness and osteoprotegerin in patients with stable coronary artery disease

Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question.