No abstract

Introduction: the causal linkCardiovascular diseases (CVDs) are a major cause of morbidity and mortality throughout the world. In the United States, CVDs affect many racial or ethnic groups, and this fact has an extremely high cost that is estimated around $200 billion annually in healthcare services, drugs, and loss of productivity. Much of this burden is due to insufficient implementation of prevention strategies and poor control of atherosclerotic cardiovascular disease (ASCVD) risk factors in many adults (1,2). According to World Health Organization data, smoking determines 10% of all CVDs (3). Tobacco smoking usage causes approximately 6 million death per year throughout the world, in the United States almost 500,000 deaths can be attributed to smoking and about 10% of these deaths are caused from second-hand smoke exposure. Epidemiologic studies have supported the assumption that cigarette smoking increases the incidence of myocardial infarction and fatal coronary artery diseases (4). The increased risk of cardiovascular events has also been shown for low-tar cigarettes and smokeless tobacco. Even passive smoking is responsible for a 30% increased risk of ASCVD, a little less than half of the risk increase in active smokers that is around 80% (5,6). Ever since the Framingham study, the epidemiologic investigations have tried to identify people with a high likelihood for a future cardiovascular events in order to make actionable interventions to reduce the risk. The concept of "risk factors" was made popular by Kannel et Review Article on Improving Outcomes in Lung Cancer Through Early Diagnosis and Smoking Cessation

In HeLa cells the expression of the BAG-3 gene, a member of the BAG family, is regulated by heavy metals and temperature, with kinetics of accumulation of mRNAs similar to Hsp70 and metallothioneins. Western blot assays performed with a polyclonal anti-BAG-3 antibody con¢rmed that higher levels of the protein were present in the cells following heat and metal exposure. By immuno£uorescence techniques and cell fractionation assays we demonstrated that following stress BAG-3 protein concentrated in the rough endoplasmic reticulum and associated with the heavy membrane fraction. The role of BAG-3 protein during apoptosis and cellular stress is discussed. ß

BAG3 protein, a member of the BAG co-chaperones family, sustains cell survival, through its interaction with the heat shock protein (HSP) 70, in a variety of normal and neoplastic cell types. bag3 gene expression is induced by stressful stimuli. Here we report for the first time that two of the three putative heat shock-responsive elements (HSEs) in bag3 promoter interact with the heat shock factor (HSF) 1 in vitro and in vivo. Furthermore, downmodulation of HSF1 protein levels by specific small interfering (si) RNAs results in reducing BAG3 protein levels, indicating that the transcription factor plays a major role in bag3 gene expression. Because of the anti-apoptotic role of BAG3 protein, these results disclose a previously unrecognized pathway, through which HSF1 maintains cell survival.