Li Yin

Epigenetics is closely related to cardiovascular diseases. Genome-wide linkage and association analyses and candidate gene approaches illustrate the multigenic complexity of cardiovascular disease. Several epigenetic mechanisms, such as DNA methylation, histone modification, and noncoding RNA, which are of importance for cardiovascular disease development and regression. Targeting epigenetic key enzymes, especially the DNA methyltransferases, histone methyltransferases, histone acetylases, histone deacetylases and their regulated target genes, could represent an attractive new route for the diagnosis and treatment of cardiovascular diseases. Herein, we summarize the knowledge on epigenetic history and essential regulatory mechanisms in cardiovascular diseases. Furthermore, we discuss the preclinical studies and drugs that are targeted these epigenetic key enzymes for cardiovascular diseases therapy. Finally, we conclude the clinical trials that are going to target some of these processes.

OBJECTIVE: Although short term prognosis has improved in patients with systemic lupus erythematosus (SLE) during the early disease course, less is known about the longterm prognosis. METHODS: A cohort of 4737 patients with a diagnostic code of SLE was identified 1964-94 in the Swedish Hospital Discharge Register and followed by linkage to the Cause of Death Register until the end of 1995. Mortality was separately analyzed in 3 different calendar periods (1964-75, 1975-84, 1985-95). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a reference. RESULTS: In total 2314 patients were deceased. Mortality was 3-fold increased (SMR = 3.63, 95% CI 3.49, 3.78) and cardiovascular disease (CVD) was the major cause of death. Patients aged 20-39 years at the first discharge had a 16-fold increased risk of death from coronary heart disease (SMR = 15.99, 95% CI 10.4, 23.6). All-cause mortality had decreased since 1975 and the reason for this decrease was entirely due to a decrease in causes attributed to SLE, but not CVD. Patients aged 20-39 years at the first discharge had a pronounced decrease in mortality, with SMR 33.59 (95% CI 24.3, 45.3) before 1975 compared with SMR 14.23 (95% CI 8.70, 22.0) after 1984. CONCLUSION: Cardiovascular disease was the major cause of death in patients with SLE and young patients had a pronounced increased risk of death. Even if all-cause mortality had declined during the last 2 decades due to causes attributed to SLE, the risk of cardiovascular death remained unchanged.

BACKGROUND: FENDRR is a long non-coding RNAs (lncRNA) that binds to polycomb repressive complexe 2 (PRC2) to epigenetically regulate the expression of its target gene. The clinical role of FENDRR in carcinomas remains yet to be found. METHOD: Real-time polymerase chain reaction (PCR) was used to examine FENDRR expression in gastric cancer cell lines/tissues compared with normal epithelial cells/adjacent non-tumorous tissues. Cell proliferation assays, Wound healing assays, and in vitro and in vivo invasion and migration assays were performed to detect the biological effects of FENDRR in gastric cancer cells. Real-time PCR, western-blot and immunohistochemistry were used to evaluate the mRNA and protein expression of fibronectin1 (FN1). Secreted matrix metalloproteinase (MMP) activities were detected and characterized using gelatin zymography assay. RESULTS: FENDRR was downregulated in gastric cancer cell lines and cancerous tissues, as compared with normal gastric epithelial cells and adjacent noncancerous tissue samples. Low FENDRR expression was correlated with deeper tumor invasion (p < 0.001), higher tumor stage (p = 0.001), and lymphatic metastasis (p = 0.007). Univariate and multivariate analyses indicated that low FENDRR expression predicted poor prognosis. Histone deacetylation was involved in the downregulation of FENDRR in gastric cancer cells. FENDER overexpression suppressed invasion and migration by gastric cancer cells in vitro, by downregulating FN1 and MMP2/MMP9 expression. CONCLUSION: Low expression of the lncRNA FENDRR occurs in gastric cancer and is associated with poor prognosis. Thus, FENDRR plays an important role in the progression and metastasis of gastric cancer.

OBJECTIVE: To assess changes in mortality in patients with rheumatoid arthritis (RA) from 1964 to 1995. METHODS: A population based cohort of 46,917 patients with RA was identified from 1964 to 1994, using the Swedish Hospital Discharge Register, and followed until 1995 through linkage to the Cause of Death Register. Mortality was separately analyzed in each inclusion period (1964-75, 1975-84, 1985-94). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a reference RESULTS: All-cause mortality was increased twice the expected (SMR = 2.03, 95% CI 2.00, 2.05). Coronary artery disease was the major cause of death and mortality was increased by 80% (SMR = 1.79, 95% CI 1.75, 1.83). Females with RA aged 20-39 at first discharge had a more than 5-fold increased risk of coronary death (SMR = 5.48, 95% CI 3.45-5.71). From 1975 patients with RA had decreasing all-cause mortality. This decline was most pronounced in patients aged 40-59 at first discharge, where SMR was 2.68 (95% CI 2.45, 2.92) from 1964 to 1974 compared to SMR 1.63 (95% CI 1.37, 1.92) from 1985 to 1994. CONCLUSION: The elevated mortality rates in RA patients compared to the general population have decreased during the last 20 years, possibly due to an increased access to specialized rheumatology care. An excess risk for death in coronary artery disease was, however, present in RA patients, especially patients with early onset of disease.