This book focuses on established cardiovascular principles and highlights some of the progress achieved by recent research in the cardiovascular field. The authors report the basic concepts related ...to the functioning of the cardiovascular system necessary for medical students to understand. To foster learning, in each chapter the fundamental points are highlighted in italics and/or bold. In addition, we have added boxes that contain some more detailed information about physiological mechanisms or clinical aspects are analyzed and described in greater detail. The book describes the structure and function of the heart and vascular system for the reader to understand how the cardiovascular system responds in both health and disease. The book conveys a unified vision of the function of the heart and the vascular system, explaining the complexity of the system that goes far beyond the integrated connection between preload, afterload and cardiac contractility. The endothelium covers the internal part of the whole cardiovascular system; therefore, endothelial physiology is treated in several chapters. Given the importance of coronary circulation in cardiac pathophysiology, this special circulation is described in detail and enriched with the most up-to-date information. Several paragraphs and boxes on clinical implications are dedicated to the principles of electrophysiology and the electrocardiogram. A space is also dedicated to myocardial ischemia/reperfusion injury and cardioprotective procedures. The book is written in a linear and simple language without compromising the scientific rigor of the various topics covered.
This book provides the readers with the latest advances and insights in the ever-expanding field of Cardio-Oncology. Specific topics discussed in the book include the potential role of inflammation ...in Cardio-Oncology and the description of the different manifestations of cardiotoxicities.
Myocardial ischemia-reperfusion injury (MIRI) is caused by several mechanisms, including the production of reactive oxygen species (ROS), altered cellular osmolarity, and inflammatory response. ...Calcium overload, altered oxygen levels, and mitochondrial ROS are also involved in these MIRI processes, resulting in the irreversible opening of the mitochondrial permeability transition pore (mPTP). These mechanisms and processes are associated with NLRP3 inflammasome priming and activation, which can also induce cell death by pyroptosis through the up-regulation of the caspase-1 pathway and IL-18 release. In addition, endothelial dysfunction, both in the presence and absence of MIRI, is also accompanied by altered oxygen levels, decreased nitric oxide production, and ROS overproduction, resulting in the expression of adhesion molecules and leukocyte infiltration in which the NLRP3 inflammasome plays a central role, thus contributing, through endothelial dysfunction, to the alteration of coronary flow, typical of ischemic heart disease. Given the intricate interrelationship between ROS and NLRP3, ROS inhibitors can reduce NLRP3 inflammasome activation, while NLRP3 inhibitors can reduce oxidative stress and inflammation. NLRP3 inhibitors have been intensively studied as anti-inflammatory agents in basic cardiovascular sciences. In this review, we analyze the interrelation between ROS and NLRP3 in ischemic heart disease and the effects of some NLRP3 inhibitors as possible therapeutic agents in this disease condition. All compounds considered in this review need larger studies to confirm their appropriate use in clinical scenarios as anti-ischemic drugs.
Reperfusion therapy is the indispensable treatment of acute myocardial infarction (AMI) and must be applied as soon as possible to attenuate the ischemic insult. However, reperfusion is responsible ...for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore (mPTP). A great part of reperfusion injury occurs during the first minute of reperfusion. The prolonged opening of mPTP is considered one of the endpoints of the cascade to myocardial damage, causing loss of cardiomyocyte function and viability. Opening of mPTP and the consequent oxidative stress due to reactive oxygen and nitrogen species (ROS/RNS) are considered among the major mechanisms of mitochondrial and myocardial dysfunction. Kinases and mitochondrial components constitute an intricate network of signaling molecules and mitochondrial proteins, which interact in response to stressors. Cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning (PostC), obtained with brief intermittent ischemia or with pharmacological agents, which drastically reduce the lethal ischemia/reperfusion injury. The protective pathways converging on mitochondria may preserve their function. Protection involves kinases, adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP modulation. Some clinical studies using ischemic PostC during angioplasty support its protective effects, and an interesting alternative is pharmacological PostC. In fact, the mPTP desensitizer, cyclosporine A, has been shown to induce appreciable protections in AMI patients. Several factors and comorbidities that might interfere with cardioprotective signaling are considered. Hence, treatments adapted to the characteristics of the patient (i.e., phenotype oriented) might be feasible in the future.
Obesity and Cardioprotection Femminò, Saveria; Pagliaro, Pasquale; Penna, Claudia
Current medicinal chemistry,
01/2020, Letnik:
27, Številka:
2
Journal Article
Recenzirano
The incidence of obesity and diabetes is increasing rapidly worldwide. Obesity and metabolic syndrome are strictly linked and represent the basis of different cardiovascular risk factors, including ...hypertension and inflammatory processes predisposing to ischemic heart disease, which represent the most common causes of heart failure. Recent advances in the understanding of ischemia/reperfusion mechanisms of injury and mechanisms of cardioprotection are briefly considered. Resistance to cardioprotection may be correlated with the severity of obesity. The observation that heart failure obese patients have a better clinical condition than lean heart failure patients is known as "obesity paradox". It seems that obese patients with heart failure are younger, making age the most important confounder in some studies. Critical issues are represented by the "obesity paradox" and heart failure exacerbation by inflammation. For heart failure exacerbation by inflammation, an important role is played by NLRP3 inflammasome, which is emerging as a possible target for heart failure condition. These critical issues in the field of obesity and cardiovascular diseases need more studies to ascertain which metabolic alterations are crucial for alleged beneficial and deleterious effects of obesity.
Nitric oxide (NO) and carbon monoxide (CO) represent a pair of biologically active gases with an increasingly well-defined range of effects on circulating platelets. These gases interact with ...platelets and cells in the vessels and heart and exert fundamentally similar biological effects, albeit through different mechanisms and with some peculiarity. Within the cardiovascular system, for example, the gases are predominantly vasodilators and exert antiaggregatory effects, and are protective against damage in myocardial ischemia-reperfusion injury. Indeed, NO is an important vasodilator acting on vascular smooth muscle and is able to inhibit platelet activation. NO reacts with superoxide anion (O
(
•)) to form peroxynitrite (ONOO(
)), a nitrosating agent capable of inducing oxidative/nitrative signaling and stress both at cardiovascular, platelet, and plasma levels. CO reduces platelet reactivity, therefore it is an anticoagulant, but it also has some cardioprotective and procoagulant properties. This review article summarizes current knowledge on the platelets and roles of gas mediators (NO, and CO) in cardioprotection. In particular, we aim to examine the link and interactions between platelets, NO, and CO and cardioprotective pathways.
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