Curcuminoids: Implication for inflammation and oxidative stress in cardiovascular diseases

Electrophiles formed during metabolic activation of chemical carcinogens and reactive oxygen species generated from endogenous and exogenous sources play a significant role in carcinogenesis. Cancer chemoprevention by induction of phase 2 proteins to counteract the insults of these reactive intermediates has gained considerable attention. Nuclear factor E2 p45-related factor 2 (Nrf2), a bZIP transcription factor, plays a central role in the regulation (basal and or inducible expression) of phase 2 genes by binding to the "antioxidant response element" in their promoters. Identification of novel Nrf2-regulated genes is likely to provide insight into cellular defense systems against the toxicities of electrophiles and oxidants and may define effective targets for achieving cancer chemoprevention. Sulforaphane is a promising chemopreventive agent that exerts its effect by strong induction of phase 2 enzymes via activation of Nrf2. In the present study, a transcriptional profile of small intestine of wild-type (nrf2 +/+) and knock out (nrf2 -/-) mice treated with vehicle or sulforaphane (9 micromol/day for 1 week, p.o.) was generated using the Murine Genome U74Av2 oligonucleotide array (representing approximately 6000 well-characterized genes and nearly 6000 expressed sequence tags). Comparative analysis of gene expression changes between different treatment groups of wild-type and nrf2-deficient mice facilitated identification of numerous genes regulated by Nrf2 including previously reported Nrf2-regulated genes such as NAD(P)H:quinone reductase (NQO1), glutathione S-transferase (GST), gamma-glutamylcysteine synthetase (GCS), UDP-glucuronosyltransferases (UGT),epoxide hydrolase, as well as a number of new genes. Also identified were genes encoding for cellular NADPH regenerating enzymes (glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and malic enzyme), various xenobiotic metabolizing enzymes, antioxidants (glutathione peroxidase, glutathione reductase, ferritin, and haptaglobin), and biosynthetic enzymes of the glutathione and glucuronidation conjugation pathways. The data were validated by Northern blot analysis and enzyme assays of selected genes. This investigation expands the horizon of Nrf2-regulated genes, highlights the cross-talk between various metabolic pathways, and divulges the pivotal role played by Nrf2 in regulating cellular defenses against carcinogens and other toxins.

Major and profound changes have taken place in China over the past 30 years. Rapid socioeconomic progress has exerted a great impact on lifestyle, ranging from food, clothing, working and living conditions, and means of transportation to leisure activities and entertainment. At the same time, new health problems have emerged, and health services are facing new challenges. Presently, cardiovascular diseases (CVD) are among the top health problems of the Chinese people, and pose a serious challenge to all engaged in the prevention and control of these diseases. An epidemic of CVD in China is emerging as a result of lifestyle changes, urbanization and longevity. Both national policy decision-making and medical practice urgently need an authoritative report which comprehensively reflects the trends in the epidemic of CVD and current preventive measures. Since 2005, guided by the Bureau of Disease Prevention of the Ministry of Health of the People's Republic of China and the National Center for Cardiovascular Diseases of China, nationwide experts in the fields of epidemiology, clinical medicine and health economics in the realms of CVD, cerebrovascular disease, diabetes and chronic kidney disease, completed the Report on Cardiovascular Diseases in China every year. The report aims to provide a timely review of the trend of the epidemic and to assess the progress of prevention and control of CVD. In addition, as the report is authoritative, representative and readable, it will become an information platform in the CVD field and an important reference book for government, academic institutes, medical organizations and clinical physicians. This publication is expected to play a positive role in the prevention and control of CVD in China. We present an abstract from the Report on Cardiovascular Diseases in China (2010), including trends in CVD, morbidity and mortality of major CVDs, up-to-date assessment of risk factors, as well as health resources for CVD, and a profile of medical expenditure, with the aim of providing evidence for decision-making in CVD prevention and control programs in China, and of delivering the most authoritative information on CVD prevention and control for all citizens. 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes. A key signaling event in this process is nuclear acetylation by histone deacetylases and p300, an intrinsic histone acetyltransferase (HAT). It has been previously shown that curcumin, a polyphenol responsible for the yellow color of the spice turmeric, possesses HAT inhibitory activity with specificity for the p300/CREB-binding protein. We found that curcumin inhibited the hypertrophy-induced acetylation and DNA-binding abilities of GATA4, a hypertrophy-responsive transcription factor, in rat cardiomyocytes. Curcumin also disrupted the p300/GATA4 complex and repressed agonist- and p300-induced hypertrophic responses in these cells. Both the acetylated form of GATA4 and the relative levels of the p300/GATA4 complex markedly increased in rat hypertensive hearts in vivo. The effects of curcumin were examined in vivo in 2 different heart failure models: hypertensive heart disease in salt-sensitive Dahl rats and surgically induced myocardial infarction in rats. In both models, curcumin prevented deterioration of systolic function and heart failure-induced increases in both myocardial wall thickness and diameter. From these results, we conclude that inhibition of p300 HAT activity by the nontoxic dietary compound curcumin may provide a novel therapeutic strategy for heart failure in humans.