Abstract: The idea of promoting angiogenesis in ischemic tissues remains an undisputed therapeutic approach for the treatment of myocardium and skeletal muscles that lack sufficient blood supply. However, clinical experiences from several large trials indicated that delivery of proangiogenic factors to patients suffering from myocardial infarction and leg ischemia has not shown significant benefits. Despite continuous success in various animal disease models, why has this simple principle not shown proof of concept in patients? What has been missing in the trial deign? What are the differences between animal models and patients? What are the optimal components for promoting functional collateral networks? This brief review discusses molecular mechanisms underlying arteriogenesis and proposes novel approaches for improvement of therapeutic outcomes. ... Read more

Abstract: Coronary artery calcification (CAC) has long been known to occur as a part of the atherosclerotic process; recently it has been shown to be an active process resembling bone formation within the vessel wall. There is good evidence that the extent of CAC reflects the total coronary atherosclerotic burden and this has generated interest in using CAC as a marker of risk. The current consensus is that large amounts of CAC identify a patient highly vulnerable to future events. The advent of CT angiography added the ability to non-invasively detect critical luminal stenoses that are associated with a more immediate risk of events, and to visualize the non-calcified component of the atherosclerotic plaque. ... Read more

Abstract: The evolution of the immune system has provided a multilevel system that interconnects the innate and adaptive immune systems to serve at least three central purposes: the defense from microbial pathogens, the capacity for discrimination of self- from non-self necessary for the prevention of autoimmune disease, and essential effector roles in wound repair and tissue remodeling. In recent studies, we have elucidated an unsuspected role for a class of naturally occurring autoreactive antibodies from the most primitive tier of B lymphocytes, which regulates fundamental functions of the innate immune system. Our findings also throw light onto long unresolved mysteries regarding the origins of the earliest waves of B lymphocyte development. ... Read more

Abstract: Metabolic syndrome is a major risk factor for cardiovascular and metabolic diseases. Playing a central role in the development of metabolic syndrome and in its clinical consequences is visceral obesity. Adipose tissue is now considered to be an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that is seen in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Recent studies have shown that obesity induces chronic local inflammation in adipose tissue, and that cells of the innate immune system, particularly macrophages, are crucially involved in adipose inflammation and systemic metabolic abnormalities. Moreover, we and others recently revealed that T cells are key regulators of adipose inflammation, and that the adaptive immune system is also crucially important. In mouse models modulation of T cell function ameliorated not only adipose inflammation but also systemic insulin resistance induced by obesity. Thus clarification of the inflammatory processes ongoing in obese adipose tissue would seem essential for the understanding of metabolic syndrome and for developing novel therapeutic strategies to treat it. ... Read more

Abstract: Historically atherosclerosis has been viewed as a disease associated with dyslipidemia because many studies (e.g., Framingham study) have demonstrated that dyslipidemia is clearly a risk factor for the disease and lipid-lowering statin therapies have proven to be highly effective in reducing the cardiovascular events and improving the quality of life for patients with coronary heart disease all over the world. Over the last decade, both preclinical and clinical research has provided multiple lines of unequivocal evidence that inflammation and immune response are integral components of the pathogenesis for atherosclerosis. In this article, both clinical and preclinical evidence in support of atherosclerosis as an inflammatory disease will be reviewed. Evidence in support of atherosclerosis as an autoimmune disease will also be presented. Furthermore, opportunities for translating the newly gained knowledge of atherosclerosis as an inflammatory/autoimmune disease into novel diagnostic and therapeutic modalities will be discussed along with challenges in developing these modalities. ... Read more

Abstract: For more than 50 years, Framingham Heart Study has produced over 1,000 scientific papers and identified major risk factors associated with heart disease, stroke, and others. It changed America's heart. Cigarettes were no longer advertised as "your doctor's favorite brands." We knew, from the Study, that LDL is a "bad" cholesterol and HDL is a good one. ... Read more

Abstract: Can one conveniently treat an autoimmune disease such as rheumatoid arthritis by ingesting the very protein that triggers the disease in the first place? The answer is maybe. Active studies are performed on both animals and humans and met with both success and failure. ... Read more

Abstract: Chemokines are small protein molecules that play a critical role in immune cell trafficking in the blood vessel lumen and within the blood vessel wall. Three such chemokines are actively involved in atherosclerosis. ... Read more

Abstract: Atherosclerosis, or the inflammation and hardening of artery walls, is the leading cause for heart attack and stroke. Finding the players that initiate and perpetuate atherosclerosis is important. Leukotrienes are among these players and present an inviting target for new drugs. ... Read more

Abstract: Do atherosclerosis and Alzheimer's disease have something in common? A new theory argues that the two diseases are independent in arising but eventually converging to one set of symptoms. The theory portends that drugs that are currently available to treat one disease can treat the other. ... Read more