Association between Blood Cadmium Levels and 10-Year Coronary Heart Disease Risk in the General Korean Population: The Korean National Health and Nutrition Examination Survey 2008–2010

<div><p>Background</p><p>Non-occupational heavy metals are considered risk factors for coronary heart disease (CHD). Several recent epidemiologic studies have evaluated the relationship between non-occupational cadmium exposure and risk factors for cardiovascular disease (CVD). This study was designed to investigate the relationship between non-occupational cadmium exposure and risk factors for CHD using the Framingham estimate of 10 year CHD risk.</p><p>Methods</p><p>The heavy metal dataset of the Korean National Health and Nutrition Examination Survey for 2008 through 2010, a cross-sectional survey of a representative sample of 4,668 non-institutionalized Koreans, was analyzed. Subjects were stratified into seven age groups to minimize the effects of age. The log-transformed blood cadmium concentrations were compared with the Framingham estimate of 10 year CHD risk in each age stratum.</p><p>Results</p><p>The Framingham estimate of 10 year CHD risk was significantly associated with the log-transformed blood cadmium concentrations (<i>p</i><0.05) in all age groups of Korean men, with the lowest regression coefficient (0.254) for men aged 20 to <35 years and the highest (3.354) for men aged 55 to <60 years; similar results, however, were not observed in Korean women. After adjusting for survey year, age, and urinary cotinine concentration, the log-transformed blood cadmium levels among men aged 20 to <35, 40 to <45, 50 to <55, and 60 to <65 years were significantly associated with systolic blood pressure (<i>p</i><0.05), but not with total and high density lipoprotein (HDL) cholesterol concentrations.</p><p>Conclusions</p><p>Cadmium exposure, even at non-occupational levels, may be associated with CHD risk in men. Despite the declines in non-occupational cadmium exposure over the past several decades, more efforts are needed.</p></div

The means and standard errors of the Framingham estimate of 10-year CHD risk by age and heavy metal quartile.

<p>All values were accounted for in study weights.</p><p>The means and standard errors of the Framingham estimate of 10-year CHD risk by age and heavy metal quartile.</p

Distribution in blood cadmium levels (µg/L) by sex.

<p>All values were accounted for in study weights.</p><p>GM: geometric mean; GSE: geometric standard error.</p><p>Distribution in blood cadmium levels (µg/L) by sex.</p

Regression coefficients of log-transformed blood cadmium levels with the Framingham estimate of 10-year CHD risk among Korean.

<p>All regression analyses were adjusted for survey year.</p><p>Results were estimated with study weights.</p><p>Regression coefficients of log-transformed blood cadmium levels with the Framingham estimate of 10-year CHD risk among Korean.</p

Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition

To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and resistance to treatment of most solid tumors, a considerable amount of effort has been made to identify HIF-1 inhibitors for treatment of cancer. Isolated from <i>Saururus cernuus</i>, manassantins A (<b>1</b>) and B (<b>2</b>) are potent inhibitors of HIF-1 activity. To define the structural requirements of manassantins for HIF-1 inhibition, we prepared and evaluated a series of manassantin analogues. Our SAR studies examined key regions of manassantin’s structure in order to understand the impact of these regions on biological activity and to define modifications that can lead to improved performance and drug-like properties. Our efforts identified several manassantin analogues with reduced structural complexity as potential lead compounds for further development. Analogues <b>MA04</b>, <b>MA07</b>, and <b>MA11</b> down-regulated hypoxia-induced expression of the HIF-1α protein and reduced the levels of HIF-1 target genes, including cyclin-dependent kinase 6 (Cdk6) and vascular endothelial growth factor (VEGF). These findings provide an important framework to design potent and selective HIF-1α inhibitors, which is necessary to aid translation of manassantin-derived natural products to the clinic as novel therapeutics for cancers

Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition

To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and resistance to treatment of most solid tumors, a considerable amount of effort has been made to identify HIF-1 inhibitors for treatment of cancer. Isolated from <i>Saururus cernuus</i>, manassantins A (<b>1</b>) and B (<b>2</b>) are potent inhibitors of HIF-1 activity. To define the structural requirements of manassantins for HIF-1 inhibition, we prepared and evaluated a series of manassantin analogues. Our SAR studies examined key regions of manassantin’s structure in order to understand the impact of these regions on biological activity and to define modifications that can lead to improved performance and drug-like properties. Our efforts identified several manassantin analogues with reduced structural complexity as potential lead compounds for further development. Analogues <b>MA04</b>, <b>MA07</b>, and <b>MA11</b> down-regulated hypoxia-induced expression of the HIF-1α protein and reduced the levels of HIF-1 target genes, including cyclin-dependent kinase 6 (Cdk6) and vascular endothelial growth factor (VEGF). These findings provide an important framework to design potent and selective HIF-1α inhibitors, which is necessary to aid translation of manassantin-derived natural products to the clinic as novel therapeutics for cancers