Doron Aronson

Bio: Doron Aronson is an academic researcher from Rambam Health Care Campus. The author has contributed to research in topics: Heart failure & Myocardial infarction. The author has an hindex of 64, co-authored 261 publications receiving 13357 citations. Previous affiliations of Doron Aronson include Boston Children's Hospital & Joslin Diabetes Center.

Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes.

Abstract: The normal aging process is often accompanied by arterial wall stiffening and by a decrease in myocardial compliance. These processes contribute to isolated systolic hypertension and diastolic heart failure, which lead to substantial morbidity and mortality among older individuals. Patients with diabetes manifest arterial stiffening and diastolic dysfunction at a younger age. This leads to the concept that the mechanism that underlies changes in vascular mechanical properties during aging is accelerated in diabetes. The Maillard reaction or advanced glycation of proteins occurs slowly in vivo with normal aging and at an accelerated rate in diabetes. Advanced glycation end-products (AGEs) that form during the Maillard reaction are implicated in the complications of aging and diabetes. The formation of AGEs on vascular wall and myocardial collagen causes cross-linking of collagen molecules to each other. This leads to the loss of collagen elasticity, and subsequently a reduction in arterial and myocardial compliance. Aminoguanidine, an inhibitor of AGE formation, is effective in slowing or preventing arterial stiffening and myocardial diastolic dysfunction in aging and diabetic animals. In aged and diabetic animals, agents that can chemically break pre-existing cross-linking of collagen molecules are capable of reverting indices of vascular and myocardial compliance to levels seen in younger or non-diabetic animals. These studies suggest that collagen cross-linking is a major mechanism that governs aging and diabetes-associated loss of vascular and cardiac compliance. The development of AGEs cross-link breakers may have important role for future therapy of isolated systolic hypertension and diastolic heart failure in these conditions.

How hyperglycemia promotes atherosclerosis: molecular mechanisms

Abstract: Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral arterial disease. Atherosclerosis accounts for virtually 80% of all deaths among diabetic patients. Prolonged exposure to hyperglycemia is now recognized a major factor in the pathogenesis of atherosclerosis in diabetes. Hyperglycemia induces a large number of alterations at the cellular level of vascular tissue that potentially accelerate the atherosclerotic process. Animal and human studies have elucidated three major mechanisms that encompass most of the pathological alterations observed in the diabetic vasculature: 1) Nonenzymatic glycosylation of proteins and lipids which can interfere with their normal function by disrupting molecular conformation, alter enzymatic activity, reduce degradative capacity, and interfere with receptor recognition. In addition, glycosylated proteins interact with a specific receptor present on all cells relevant to the atherosclerotic process, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells. The interaction of glycosylated proteins with their receptor results in the induction of oxidative stress and proinflammatory responses 2) oxidative stress 3) protein kinase C (PKC) activation with subsequent alteration in growth factor expression. Importantly, these mechanisms may be interrelated. For example, hyperglycemia-induced oxidative stress promotes both the formation of advanced glycosylation end products and PKC activation.

Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes.

Abstract: Total GLUT4 content in skeletal muscle from individuals with type 2 diabetes is normal; however, recent studies have demonstrated that translocation of GLUT4 to the plasma membrane is decreased in response to insulin stimulation. It is not known whether physical exercise stimulates GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes. Five subjects (two men, three women) with type 2 diabetes and five normal control subjects (5 men), as determined by a standard 75-g oral glucose tolerance test, were recruited to determine whether an acute bout of cycle exercise activates the translocation of GLUT4 to the plasma membrane in skeletal muscle. Each subject had two open biopsies of vastus lateralis muscle; one at rest and one 3-6 weeks later from the opposite leg after 45-60 min of cycle exercise at 60-70% of VO2max. Skeletal muscle plasma membranes were prepared by subcellular fractionation, and GLUT4 content was determined by Western blotting. Plasma membrane GLUT4 increased in each subject in response to exercise. The mean increase in plasma membrane GLUT4 for the subjects with type 2 diabetes was 74 +/-20% above resting values, and for the normal subjects the increase was 71+/-18% above resting values. Although plasma membrane GLUT4 content was approximately 32% lower at rest and after exercise in the muscle of the subjects with type 2 diabetes, the differences were not statistically significant. We conclude that in contrast to the previously reported defect in insulin-stimulated GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes, a single bout of exercise results in the translocation of GLUT4 to the plasma membrane in skeletal muscle of individuals with type 2 diabetes. These data provide the first direct evidence that GLUT4 translocation is an important cellular mechanism through which exercise enhances skeletal muscle glucose uptake in individuals with type 2 diabetes.

Relation between red cell distribution width and clinical outcomes after acute myocardial infarction.

Abstract: Increased red blood cell distribution width (RDW) has been associated with adverse outcomes in heart failure and stable coronary disease. We studied the association between baseline RDW and changes in RDW during hospital course with clinical outcomes in patients with acute myocardial infarction (AMI). Baseline RDW and RDW change during hospital course were determined in 1,709 patients with AMI who were followed for a median of 27 months (range 6 to 48). The relation between RDW and clinical outcomes after hospital discharge were tested using Cox regression models, adjusting for clinical variables, baseline hemoglobin, mean corpuscular volume, and left ventricular ejection fraction. Compared to patients in the first RDW quintile, the adjusted hazard ratios for death progressively increased with higher quintiles of RDW (second quintile 1.1, 95% confidence interval [CI] 0.6 to 2.1; third quintile 1.8, 95% CI 1.0 to 3.2; fourth quintile 2.0, 95% CI 1.1 to 3.4; fifth quintile 2.8, 95% CI 1.6 to 4.7, p for trend <0.0001). An increase in RDW during hospital course was also associated with subsequent mortality (adjusted hazard ratio 1.13 for 1-SD increase in RDW, 95% CI 1.02 to 1.25). Similar results were obtained for the end point of heart failure. The association between increased RDW and worse outcome was evident in patients with and without anemia. In conclusion, there is a graded, independent association between increased RDW and mortality after AMI. An increase in RDW during hospitalization also portends adverse clinical outcome.

Diagnosis and Management of the Metabolic Syndrome An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

Abstract: The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …

ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation

Abstract: ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ADP : adenosine diphosphate AF : atrial fibrillation AMI : acute myocardial infarction AV : atrioventricular AIDA-4 : Abciximab Intracoronary vs. intravenously Drug Application APACHE II : Acute Physiology Aand Chronic

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)

Abstract: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).