Intermedin protects against myocardial ischemia-reperfusion injury in diabetic rats.

BACKGROUND: Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown. METHODS: Diabetes was induced by streptozotocin in Sprague--Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation. RESULTS: IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 +/- 4.84 pmol/L, p \u3c 0.05) and myocardial tissue (9.8 +/- 0.60 pmol/L, p \u3c 0.01) compared to pre-MI control values (43.62 +/- 3.47 pmol/L and 4.4 +/- 0.41). IMD administration to diabetic rats subjected to MI/R decreased oxidative stress product generation, apoptosis, infarct size, and inflammatory cytokine release (p \u3c 0.05 or p \u3c 0.01). CONCLUSIONS: By reducing oxidative stress, inflammation, and apoptosis, IMD may represent a promising novel therapeutic target mitigating diabetic ischemic heart injury

Prevalence and risk factors of abnormal left ventricular geometrical patterns in untreated hypertensive patients

BACKGROUND: The various prevalence of LVH and abnormal LV geometry have been reported in different populations. So far, only a few reports are available on the prevalence of LV geometric patterns in a large Chinese untreated hypertensive population. METHODS: A total of 9,286 subjects (5167 men and 4119 women) completed the survey and 1641 untreated hypertensive patients (1044 males and 597 females) enrolled in the present study. The LV geometry was classified into four patterns: normal; abnormal,defined as concentric remodeling;concentric or eccentric hypertrophy based on the values of left ventricular mass index (LVMI) and relative wall thickness (RWT). Logistic regression model was applied to determine the odds ratio (OR) and 95% confidence intervals (CI) of the risk factors of left ventricular hypertrophy. RESULTS: The prevalence of LVH was 20.2% in untreated hypertensive patients, much higher in women (30.8%) than in men (14.2%) (P < 0.01). The prevalence of LV geometrical patterns was 34.9%, 11.1%, 9.1% for concentric remodeling, concentric and eccentric hypertrophy,respectively. After adjustment by using Logistic regression model, the risk factors for LVH and abnormal LV geometry were age, female, systolic blood pressure, and body mass index. And low high density lipoprotein maybe a positive factor. CONCLUSIONS: The prevalence of LVH and abnormal LV geometric patterns was higher in women than in men and increased with age. It is crucial to improve the awareness rate of hypertension and control the risk factors of CV complications in untreated hypertensive population

SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

Background. Sirtuin 1 (SIRT1) is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII-) induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs) to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury

IFN Regulatory Factor-1 Modulates the Function of Dendritic Cells in Patients with Acute Coronary Syndrome

Background: Atherosclerosis is widely recognized as a complex inflammatory disease involving pathogenic immune response of T cells and antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. Accumulating evidence has revealed that mature DCs play critical roles in the differentiation of effector T cells into CD4+ T cells, which effectively participate in the onset of acute coronary syndrome (ACS). IFN regulatory factor (IRF)-1 has been shown to be involved in various immune processes. The role of IRF-1 in DCs in the pathogenesis of ACS has not been investigated. Methods and Results: We examined the relative mRNA and protein expression of IRF-1 in human monocyte-derived DCs in patients with coronary artery disease (CAD). The overexpression or silencing of IRF-1 expression in DCs in patients with ACS was performed to explore the possible role of IRF-1 in the maturation and function of DCs involved in ACS. The results showed that the relative expression of IRF-1 in DCs is obviously increased in patients with ACS. The overexpression or silencing of IRF-1 expression could effectively promote or attenuate the maturation and function of DCs. In addition, we revealed that the MAPK pathway (phosphorylation of JNK, p38 and ERK1/2) might be downstream of IRF-1 signalling pathway in activation of circulating DCs in ACS patients. Conclusion: The present data demonstrate that IRF-1 could effectively promote the immune maturation and function of DCs in ACS patients

Effects of replacement of corn silage and distillers' grain diets with hay during prepartum on the health and production performance of dairy heifers postpartum

In this study, we aimed to comprehensively evaluate the effects of prepartum replacement of corn silage and distillers' grain diets with hay on the postpartum health and production performance in dairy heifers. Pregnant Holstein dairy heifers were randomly assigned to two groups and fed different diets with the same net energy and protein concentrations. The low corn silage plus hay (CH) group diet mainly contained oat hay (28.5%), corn silage (25%) and folium ginkgo (23%). The high corn silage plus distillers' grains (CD) group diet contained corn silage (53.5%), distillers' grains (5%) and folium ginkgo (18%). Dairy heifers were fed from the beginning of pregnancy to the end of the transition period. Calf birthweight, postpartum morbidity, milk production and reproductive performance were determined. Compared with the cows in the CH group, those in the CD group presented increased calf birthweight and a high risk of some postpartum disorders (p &lt; 0.05), particularly ketosis (37.63% vs. 24.54%) and retained placenta (9.41% vs. 3.92%). However, there was no difference between the groups in reproductive performance, including first timed artificial insemination (TAI) rate, date of TAI and conception rate of TAI. The lactation curves showed no difference in milk yield during the peak lactation period of primiparous cows between the CH and CD groups; the total milk production was 33.39 kg and 33.19 kg respectively. Notably, the time to peak milk production was delayed in the CD group. It can be concluded that replacing corn silage and distillers' grains with hay can reduce postpartum morbidity in dairy heifers and shorten the time to peak milk production

Angiotensin-(1-7) Attenuates Angiotensin II-Induced ICAM-1, VCAM-1, and MCP-1 Expression via the MAS Receptor Through Suppression of P38 and NF-&#954;B Pathways in HUVECs

Background/Aims: Atherosclerosis is a chronic inflammatory disease. Intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) play important roles in inflammatory processes. P38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-&#954;B signaling regulate ICAM-1, VCAM-1, and MCP-1 expression. Angiotensin (Ang) II upregulates ICAM-1, VCAM-1, and MCP-1 expression through the P38 MAPK and NF-&#954;B pathways. Ang-(1-7) may oppose the actions of Ang II. We investigated whether Ang-(1-7) prevents Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression in human umbilical vein endothelial cells (HUVECs). Methods: ICAM-1, VCAM-1, and MCP-1 expression was estimated by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA); P38, NF-&#954;B, and p-I&#954;B-a expression was estimated by western blotting. Results: Ang-(1-7) inhibited Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression and secretion in HUVECs. Ang II sharply increased P38 MAPK phosphorylation, which was inhibited by pretreatment with Ang-(1-7). Moreover, Ang-(1-7) significantly inhibited Ang II-induced I&#954;B-a phosphorylation and NF-&#954;B P65 nuclear translocation. The MAS receptor antagonist A-779 abolished the suppressive effects of Ang-(1-7). Conclusion: Ang-(1-7) attenuates Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression via the MAs receptor by suppressing the P38 and NF-&#954;B pathways in HUVECs. Ang-(1-7) might delay the progression of inflammatory diseases, including atherosclerosis

Both β1- and β2-adrenoceptors contribute to feedforward coronary resistance vessel dilation during exercise

During exercise, β-feedforward coronary vasodilation has been shown to contribute to the matching of myocardial oxygen supply with the demand of the myocardium. Since both β1- and β2-adrenoceptors are present in the coronary microvasculature, we investigated the relative contribution of these subtypes to β-feedforward coronary vasodilation during exercise as well as to infusion of the β1-agonist norepinephrine and the β1- and β2-agonist isoproterenol. Chronically instrumented swine were studied at rest and during graded treadmill exercise (1-5 km/h) under control conditions and after β1-blockade with metoprolol (0.5 mg/kg iv) and β1/β2-blockade with propranolol (0.5 mg/kg iv). The selectivity and degree of β-blockade of metoprolol and propranolol were confirmed using isoproterenol infusion (0.05-0.4 μg· kg-1·min-1) under resting conditions. Isoproterenol-induced coronary vasodilation was mediated through the β2-adrenoceptor, whereas norepinephrine-induced coronary vasodilation was principally mediated through the β1- adrenoceptor. Exercise resulted in a significant increase in left ventricular norepinephrine release and epinephrine uptake. β1-Adrenoceptor blockade with metoprolol had very little effect under resting conditions. However, during exercise, metoprolol attenuated the increase in myocardial oxygen supply in excess of the reduction in myocardial oxygen demand, as evidenced by a progressive decrease in coronary venous PO2. Consequently, metoprolol caused a clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous PO2. Additional β2-adrenoceptor blockade with propranolol further inhibited myocardial oxygen supply during exercise, resulting in a further clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous PO2. In conclusion, both β1- and β2-adrenoceptors contribute to the β-feedforward coronary resistance vessel dilation during exercise. Copyrigh