Christodoulos Stefanadis

Bio: Christodoulos Stefanadis is an academic researcher from Yale University. The author has contributed to research in topics: Coronary artery disease & Myocardial infarction. The author has an hindex of 18, co-authored 32 publications receiving 1387 citations. Previous affiliations of Christodoulos Stefanadis include Athens State University & National and Kapodistrian University of Athens.

Mitochondria and cardiovascular diseases-from pathophysiology to treatment.

Abstract: Mitochondria are the source of cellular energy production and are present in different types of cells. However, their function is especially important for the heart due to the high demands in energy which is achieved through oxidative phosphorylation. Mitochondria form large networks which regulate metabolism and the optimal function is achieved through the balance between mitochondrial fusion and mitochondrial fission. Moreover, mitochondrial function is upon quality control via the process of mitophagy which removes the damaged organelles. Mitochondrial dysfunction is associated with the development of numerous cardiac diseases such as atherosclerosis, ischemia-reperfusion (I/R) injury, hypertension, diabetes, cardiac hypertrophy and heart failure (HF), due to the uncontrolled production of reactive oxygen species (ROS). Therefore, early control of mitochondrial dysfunction is a crucial step in the therapy of cardiac diseases. A number of anti-oxidant molecules and medications have been used but the results are inconsistent among the studies. Eventually, the aim of future research is to design molecules which selectively target mitochondrial dysfunction and restore the capacity of cellular anti-oxidant enzymes.

Vasa vasorum imaging: A new window to the clinical detection of vulnerable atherosclerotic plaques

Abstract: Complications of vulnerable atherosclerotic plaques (rupture, luminal and mural thrombosis, intraplaque hemorrhage, rapid progression to stenosis, spasm, and so forth) lead to heart attacks and strokes. It remains difficult to identify what plaques are vulnerable to these complications. Despite recent developments such as thermography, spectroscopy, and magnetic resonance imaging, none of them is approved for clinical use. Intravascular ultrasound (IVUS), a relatively old yet widely available clinical tool for guiding intracoronary procedures, is increasingly used for characterization of atherosclerotic plaques. However, inability of IVUS in measuring plaque activity limits its value in detection of vulnerable plaques. In this review, we present new information suggesting that microbubble contrast-enhanced IVUS can measure activity and inflammation within atherosclerotic plaques by imaging vasa vasorum density. An increasing body of evidence indicates that vasa vasorum density may be a strong marker for plaque vulnerability. We suggest that a combination of structural assessment (cap thickness, lipid core, calcification, etc) and vasa vasorum density imaging by IVUS can serve as the most powerful clinically available tool for characterization of vulnerable plaques. Due to space limitations, all IVUS images and movies are posted on the website of the Ultimate IVUS Collaborative Project: http://www.ultimateivus.com.

Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

Abstract: It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives

Abstract: Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.

Inflammation as a cardiovascular risk factor.

Abstract: Inflammation occurs in the vasculature as a response to injury, lipid peroxidation, and perhaps infection. Various risk factors, including hypertension, diabetes, and smoking, are amplified by the harmful effects of oxidized low-density-lipoprotein cholesterol, initiating a chronic inflammatory reaction, the result of which is a vulnerable plaque, prone to rupture and thrombosis. Epidemiological and clinical studies have shown strong and consistent relationships between markers of inflammation and risk of future cardiovascular events. Inflammation can potentially be detected locally by imaging techniques as well as emerging techniques, such as identification of temperature or pH heterogeneity. It can be detected systemically by measurement of inflammatory markers. Of these, the most reliable and accessible for clinical use is currently high-sensitivity C-reactive protein. A combination of methods may provide the best identification of persons at risk for cardiovascular events who would benefit from treatment. In randomized, controlled trials, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the form of statins, have been shown to provide effective therapy for lowering CRP, in conjunction with their lipid-lowering effects. Although the magnitude of risk reduction associated with statin use appears to be largest for those with the highest serum levels of CRP, whether CRP reduction per se lowers cardiovascular risk is unknown.