Environment-Gene interaction in common complex diseases: New approaches

Approximately 100,000 different environmental chemicals that are in use as high production volume chemicals confront us in our daily lives. Many of the chemicals we encounter are persistent and have long half-lives in the environment and our bodies. These compounds are referred to as Persistent Organic Pollutants, or POPS. The total environment however is broader than just toxic pollutants. It includes social capital, social economic status, and other factors that are not commonly considered in traditional approaches to studying environment-human interactions. The mechanism of action of environmental agents in altering the human phenotype from health to disease is more complex than once thought. The focus in public health has shifted away from the study of single-gene rare diseases and has given way to the study of multifactorial complex diseases that are common in the population. To understand common complex diseases, we need teams of scientists from different fields working together with common aims. We review some approaches for studying the action of the environment by discussing use-inspired research, and transdisciplinary research approaches. The Genomic era has yielded new tools for study of gene-environment interactions, including genomics, epigenomics, and systems biology. We use environmentally-driven diabetes mellitus type two as an example of environmental epigenomics and disease. The aim of this review is to start the conversation of how the application of advances in biomedical science can be used to advance public health

Atherosclerotic vascular disease conference: Executive summary: Atherosclerotic vascular disease conference proceeding for healthcare professionals from a special writing group of the American Heart Association

Atherosclerosis is one of the most important and common causes of death and disability in the United States and throughout the world. More than 25 million persons in the United States have at least one clinical manifestation of atherosclerosis, and in many more, atherosclerosis remains an occult but important harbinger of significant cardiovascular events. Throughout the last half of the past century, coronary artery atherosclerosis has been a major focus for basic and clinical investigation. As a result, considerable strides have been made in the development of programs to prevent and treat the clinical manifestations of coronary artery disease. The development of lipid-lowering, antithrombotic, thrombolytic, and catheter-based therapies in particular has had considerable impact in reducing death and disability from coronary atherosclerosis. Yet atherosclerosis is a systemic disease with important sequelae in many other regional circulations, including those supplying the brain, kidneys, mesentery, and limbs. Persons with cerebral atherosclerosis are at increased risk for ischemic stroke. Those with renal artery atherosclerosis are at risk for severe and refractory hypertension as well as renal failure. Patients with atherosclerosis affecting the limb, ie, peripheral arterial disease (PAD), can develop disabling symptoms of claudication or critical limb ischemia and its associated threat to limb viability. Moreover, once disease is apparent in one vascular territory, there is increased risk for adverse events in other territories. For example, patients with PAD have a 4-fold greater risk of myocardial infarction and a 2- to 3-fold greater risk of stroke than patients without PAD

Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37ºC). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 µM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system