Cardiac Fibroblast-Specific Activating Transcription Factor 3 Promotes Myocardial Repair after Myocardial Infarction / 中华医学杂志(英文版)

<p><b>Background</b>Myocardial ischemia injury is one of the leading causes of death and disability worldwide. Cardiac fibroblasts (CFs) have central roles in modulating cardiac function under pathophysiological conditions. Activating transcription factor 3 (ATF3) plays a self-protective role in counteracting CF dysfunction. However, the precise function of CF-specific ATF3 during myocardial infarction (MI) injury/repair remains incompletely understood. The aim of this study was to determine whether CF-specific ATF3 affected cardiac repair after MI.</p><p><b>Methods</b>Fifteen male C57BL/6 wild-type mice were performed with MI operation to observe the expression of ATF3 at 0, 0.5, 1.0, 3.0, and 7.0 days postoperation. Model for MI was constructed in ATF3TGfl/flCol1a2-Cre+ (CF-specific ATF3 overexpression group, n = 5) and ATF3TGfl/flCol1a2-Cre- male mice (without CF-specific ATF3 overexpression group, n = 5). In addition, five mice of ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre- were subjected to sham MI operation. Heart function was detected by ultrasound and left ventricular remodeling was observed by Masson staining (myocardial fibrosis area was detected by blue collagen deposition area) at the 28 day after MI surgery in ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre- mice received sham or MI operation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect cell proliferation/cell cycle-related gene expression in cardiac tissue. BrdU staining was used to detect fibroblast proliferation.</p><p><b>Results</b>After establishment of an MI model, we found that ATF3 proteins were increased in the heart of mice after MI surgery and dominantly expressed in CFs. Genetic overexpression of ATF3 in CFs (ATF3TGfl/flCol1a2-Cre+ group) resulted in an improvement in the heart function as indicated by increased cardiac ejection fraction (41.0% vs. 30.5%, t = 8.610, P = 0.001) and increased fractional shortening (26.8% vs. 18.1%, t = 7.173, P = 0.002), which was accompanied by a decrease in cardiac scar area (23.1% vs. 11.0%, t = 8.610, P = 0.001). qRT-PCR analysis of CFs isolated from ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre- ischemic hearts revealed a distinct transcriptional profile in ATF3-overexpressing CFs, displaying pro-proliferation properties. BrdU-positive cells significantly increased in ATF3-overexpressing CFs than control CFs under angiotensin II stimuli (11.5% vs. 6.8%, t = 31.599, P = 0.001) or serum stimuli (31.6% vs. 20.1%, t = 31.599, P = 0.001). The 5(6)-carboxyfluorescein N-hydroxysuccinimidyl ester assay showed that the cell numbers of the P2 and P3 generations were higher in the ATF3-overexpressing CFs at 24 h (P2: 91.6% vs. 71.8%, t = 8.465, P = 0.015) and 48 h (P3: 81.6% vs. 51.1%, t = 9.029, P = 0.012) after serum stimulation. Notably, ATF3 overexpression-induced CF proliferation was clearly increased in the heart after MI injury.</p><p><b>Conclusions</b>We identify that CF-specific ATF3 might contribute to be MI repair through upregulating the expression of cell cycle/proliferation-related genes and enhancing cell proliferation.</p>

Impact of cardiovascular disease deaths on life expectancy in Chinese population / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We aimed to analyze the impact of cardiovascular disease (CVD) deaths on life expectancy (LE) in Chinese population and estimate the percentage reduction in CVD mortality needed to increase LE by 1 year from the current level, a national target of health improvement.</p><p><b>METHODS</b>We used life tables, cause-elimination life tables, and age decomposition of LE with corrected mortality data from the National Disease Surveillance System in 2010.</p><p><b>RESULTS</b>LE at birth of Chinese people was 73.24 years in 2010. Women had a longer LE than men, and urban population had a longer LE than rural population. CVD deaths resulted in a 4.79-year LE loss and premature deaths in people aged 25 to 64 years were responsible for a substantial part of LE loss from CVD. Death from ischemic heart disease and cerebrovascular diseases accounted for 69.2% of LE loss from CVD deaths and death from cerebrovascular diseases was the largest contributor. In rural men, 51.1% LE loss from CVD deaths was caused by cerebrovascular diseases. If there were no changes in mortality rates for all other diseases, a 27.4% reduction in CVD mortality would increase LE by 1 year in Chinese population.</p><p><b>CONCLUSION</b>There is a considerable impact of CVD deaths on LE. A 1-year LE increase in the future requires at least a 27.4% reduction in CVD mortality from the current level. Targeting the rural population and tackling cerebrovascular diseases are important for reaching the national goal of health improvement.</p>

Impact of cerebrovascular disease mortality on life expectancy in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the impact of cerebrovascular disease mortality on life expectancy (LE) in China in 2010 compared with 2005, and to identify the high-risk population (age, sex, and region) where cerebrovascular disease mortality has had a major impact on LE.</p><p><b>METHODS</b>LE and cause-eliminated LE were calculated by using standard life tables which used adjusted mortality data from the Death Surveillance Data Sets in 2005 and 2010 from the National Disease Surveillance System. Decomposition was used to quantitate the impact of cerebrovascular disease in different age groups.</p><p><b>RESULTS</b>LE in China was 73.24 years in 2010, which was higher in women and urban residents compared with men and rural residents. The loss of LE caused by cerebrovascular disease mortality was 2.26 years, which was higher in men and rural residents compared with women and urban residents. More than 30% of the loss of LE were attributed to premature death from cerebrovascular disease in people aged <65 years. Compared with 2005, LE in 2010 increased by 0.92 years. The reduction of cerebrovascular disease mortality in urban residents contributed 0.45 years to the increase of LE, but the increase of cerebrovascular disease mortality caused a 0.12-year loss of LE in rural residents.</p><p><b>CONCLUSION</b>Cerebrovascular disease mortality had a major impact on LE in China, with a significant difference between urban and rural residents. LE is likely to be further increased by reducing cerebrovascular disease mortality, and special attention should be paid to reducing premature deaths in people aged <65 years.</p>