Effect of mitochondrial tRNA(Lys) mutation on the clinical and biochemical characteristics of Chinese essential hypertensive subjects.

Mitochondrial dysfunction has been potentially implicated in both human and experimental hypertension. We performed the mutational analysis of tRNA(Lys) gene by PCR amplification and subsequent sequence analysis of the PCR fragments from 990 Chinese essential hypertensive subjects. We also made a comparative analysis of the collected data of the essential hypertension subjects who carried tRNA(Lys) mutation and those who did not carry the mutation using the methods of 1:1 case-control study. We totally found 7 mutation sites in 10 subjects. The onset ages of the individuals carrying the mutation were earlier than those who did not bear them. The level of blood urea nitrogen in hypertension subjects who carried tRNA(Lys) mutation was higher than the hypertension subjects who did not carried tRNA(Lys) mutation, while the serum potassium was significantly lower. The level of platelet count in hypertension subjects who carried tRNA(Lys) mutation was lower. The level of ventricular septal thickness in hypertension subjects who carried tRNA(Lys) mutation was higher and the level of left ventricular end diastolic diameter in hypertension subjects was significantly lower. Mitochondrial tRNA(Lys) mutations might result in the change of their structure and function, and then damaged the blood metabolism, the balance of the blood electrolyte, the steady-state of the blood cells and the heart structure and function, which were involved in the progress of the essential hypertension. Part of the essential hypertension patients clinically presented the characters of maternal inheritance, which might be associated with the tRNA(Lys) mutation.

Association of serum lipids with arterial stiffness in a population-based study in Beijing.

BACKGROUND: Some cardiovascular risk factors such as age, hypertension and diabetes have been confirmed to be positively correlated with arterial stiffness. However, the relationship between serum lipids and arterial stiffness is incompletely understood. Recent studies have been far from conclusive and consistent data were not obtained. We investigated the relationship between serum lipids and pulse wave velocity (PWV) in community-dwelling individuals in Beijing, China. METHODS: This was a population-based, cross-sectional sample of adults (n = 2375; 48·1% men; age range, 40-96 years) from two communities in Beijing. A questionnaire was used for the risk factors of arterial stiffness. Anthropometry, blood pressure and heart rate were measured. Values of fasting plasma glucose (FPG), serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and uric acid were measured. Carotid-femoral PWV (cfPWV) and carotid-radial PWV (crPWV) were assessed non-invasively. RESULTS: Carotid-femoral pulse wave velocity was significantly positively related to TC (r = 0·221; P < 0·0001), LDL-C (r = 0·193; P < 0·0001) and inversely related to HDL-C (r = -0·240; P < 0·0001), but not with TG (r = 0·073; P = 0·6721). crPWV was inversely related to HDL-C (r = -0·272; P < 0·0001), but not with TC (r = 0·007; P = 0·4781), LDL-C (r = 0·021; P = 0·6393) or TG (r = 0·008; P = 0·2498). The multiple regression analysis showed that LDL-C was independently associated with cfPWV and that HDL-C was inversely associated with cfPWV and crPWV. TC and TG were not independently related to cfPWV and crPWV. CONCLUSIONS: These data show the correlation between some of the parameters of serum lipids and arterial stiffness. LDL-C was independently associated with aortic stiffness, and HDL-C was independently inversely associated with aortic stiffness and peripheral stiffness.

Effects of omega-3 fatty acid for sudden cardiac death prevention in patients with cardiovascular disease: a contemporary meta-analysis of randomized, controlled trials.

PURPOSE: Experimental and epidemiological studies suggest that omega-3 fatty acids have an antiarrhythmic effect. However, evidence from randomized controlled trials (RCTs) for prevention of sudden cardiac death (SCD) remains controversial. This study sought to evaluate the efficacy of omega-3 fatty acids for secondary prevention of SCD in patients with cardiovascular disease (CVD) in the era of guidelines-based therapy. METHODS: We conducted a PubMed/EMBASE/CENTRAL search for RCTs evaluating omega-3 fatty acids for CVD secondary prevention with at least 6 months follow-up and with data on SCD. Primary outcome was SCD. Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS: Ten randomized controlled trials were identified evaluating a total of 33,429 patients with CVD. In patients with guidelines-adjusted therapy, omega-3 fatty acids did not reduce the risk ratio (RR) of SCD (RR:0.96; 95% CI: 0.84-1.10). In patients with non- guidelines-adjusted therapy, omega-3 fatty acids reduced the RR of SCD (RR: 0.64; 95% CI: 0.51-0.80). Overall, RR for cardiac death and all-cause mortality were 0.81 (95% CI: 0.69-0.95) and 0.89 (95% CI: 0.79-1.01), respectively. CONCLUSIONS: In the era of guidelines-adjusted treatment for CVD secondary prevention, omega-3 fatty acids do not appear to reduce SCD.

Association between high-sensitivity cardiac troponin T and N-terminal pro-brain natriuretic peptide in a community based population.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury. However, it remains unclear whether subclinical myocardial injury is associated with NT-proBNP elevation in a community based population. METHODS: In a community based study, levels of hs-cTnT and of NT-proBNP were determined in 1 497 participants older than 45 years. The lower detection limit of the hs-cTnT assay used in the present study was 0.003 ng/ml. The association of hs-cTnT levels and NT-proBNP levels was analyzed. RESULTS: When the subjects with undetectable (<0.003 ng/ml), intermediate (0.003-0.014 ng/ml), and elevated (≥0.014 ng/ml) levels of hs-cTnT were compared (r = 0.175, P < 0.001), a strong association between the hs-cTnT levels and NT-proBNP levels was observed (ß = -0.206, P < 0.001; ß = -0.118, P < 0.001, respectively). In multivariable analyses, older age and hs-cTnT were positively and independently associated with NT-proBNP levels (ß = 0.341, P < 0.001; ß = 0.143, P < 0.001, respectively), and male gender and the levels of eGFR were inversely and independently associated with NT-proBNP levels. When the subjects with normal or elevated NT-proBNP were analyzed separately, the hs-cTnT level was not an independent predictor for the NT-proBNP level in the normal NT-proBNP group, whereas the hs-cTnT level was the only independent predictor for NT-proBNP level in the elevated NT-proBNP group (ß = 0.399, P < 0.01). CONCLUSIONS: In this community based population, NT-proBNP elevation was common. In addition to female gender and older age, subclinical myocardial injury indicated by the hs-cTnT level was another important factor in NT-proBNP elevation.

Prognostic abilities of different calculation formulas for the glomerular filtration rate in elderly Chinese patients with coronary artery disease.

OBJECTIVE: As a standard indicator of renal function, the glomerular filtration rate (GFR) is vital for the prognostic analysis of elderly patients with coronary artery disease (CAD). Thus, the search for the calculation equation of GFR with the best prognostic ability is an important task. The most commonly used Modification of Diet in Renal Disease (MDRD) equation and the Chinese version (CMDRD) of the MDRD equation has many shortcomings. The newly developed Mayo Clinic quadratic (Mayo) and Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) equations may overcome these shortcomings. Because the populations involved in these equation-related studies are almost completely devoid of subjects > 70 years of age, there are more debates on the performance of these equations in the elderly. This study was designed to compare the prognostic abilities of different calculation formulas for the GFR in elderly Chinese patients with CAD. METHODS: This study included 1050 patients (≥60 years of age) with CAD. The endpoint was all-cause mortality over a mean follow-up period of 417 days. RESULTS: The median age was 86 years (60-104 years). The median values for the MDRD-GFR, CMDRD-GFR, CKD-EPI-GFR, and Mayo-GFR were 66.0, 69.2, 65.6, and 75.8 mL/minute/1.73 m(2), respectively. The prevalence of GFR < 60 mL/minute/1.73 m(2) based on these measures was 39.3%, 35.4%, 43.0%, and 28.7%, respectively. Their area under the curve values for predicting death were 0.611, 0.610, 0.625, and 0.632, respectively. Their cut-off points for predicting death were 54.1, 53.5, 48.0, and 57.4 mL/minute/1.73 m(2), respectively. Compared with the MDRD-GFR, the net reclassification improvement values of the CMDRD-GFR, CKD-EPI-GFR, and Mayo-GFR were 0.02, 0.10, and 0.14, respectively. CONCLUSION: The prognostic abilities of the CKD-EPI and Mayo equations were significantly superior to the MDRD and CMDRD equations; the Mayo equation had a mild, but not statistically significant superiority compared with the CKD-EPI equation in elderly Chinese patients with CAD.

The ability of NT-proBNP to detect chronic heart failure and predict all-cause mortality is higher in elderly Chinese coronary artery disease patients with chronic kidney disease.

OBJECTIVE: To analyze the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and renal function, and compare the ability and cut-off thresholds of NT-proBNP to detect chronic heart failure (CHF) and predict mortality in elderly Chinese coronary artery disease (CAD) patients with and without chronic kidney disease (CKD). METHODS: The study included 999 CAD patients older than 60 years. The endpoint was all-cause mortality over a mean follow-up period of 417 days. RESULTS: The median age was 86 years (range: 60-104 years), and the median NT-proBNP level was 409.8 pg/mL. CKD was present in 358 patients. Three hundred and six patients were positive for CHF. One hundred and ten CKD patients and 105 non-CKD patients died. Not only CKD, but also estimated glomerular filtration rate independently affected NT-proBNP. NT-proBNP detected CHF with a cut-off value of 298.4 pg/mL in non-CKD patients and a cut-off value of 435.7 pg/mL in CKD patients. NT-proBNP predicted death with a cut-off value of 369.5 pg/mL in non-CKD patients and a cut-off value of 2584.1 pg/mL in CKD patients. The NT-proBNP level was significantly related to the prevalence of CHF and all-cause mortality in CAD patients with and without CKD; this effect persisted after adjustment. The crude and multiple adjusted hazard ratios of NT-proBNP to detect CHF and predict mortality were significantly higher in patients with CKD compared with the remainder of the population. The addition of NT-proBNP to the three-variable and six-variable models generated a significant increase in the C-statistic. CONCLUSION: Amongst elderly Chinese CAD patients, there was an independently inverse association between NT-proBNP and renal function. With the higher cutoff points, NT-proBNP better detected CHF and better predicted mortality in CKD patients than in non-CKD patients.

Association of high-density lipoprotein cholesterol with the estimated glomerular filtration rate in a community-based population.

BACKGROUND: Reduced kidney function is independently associated with low high-density lipoprotein cholesterol (HDL-C) levels in patients with end-stage renal disease (ESRD), those on hemodialysis, and those with stage 3-5 chronic kidney disease (CKD). However, epidemiological data investigating the relationship between HDL-C levels and kidney function in the general population with roughly normal kidney function are limited, and the results are also inconsistent. The aim of this study was to evaluate the relationship between HDL-C levels and the estimated glomerular filtration rate (eGFR) in a community-based population in China. METHODS: This was a community-based cross-sectional survey. In total, 4925 participants (age range, 18-96 years; mean, 51.30±11.98 years) were recruited during routine health status examinations. A questionnaire was used to ascertain age, smoking status, and the history of hypertension and diabetes mellitus for each participant. We measured the body mass index, waist circumference, systolic and diastolic blood pressure, and fasting glucose, total cholesterol, triglyceride, HDL-C, low-density lipoprotein cholesterol, uric acid, and serum creatinine level of each participant. eGFR was evaluated using the Chinese modified Modification of Diet in Renal Disease equation. RESULTS: The HDL-C level was higher in the first quartile (lowest quartile) of eGFR than in the fourth quartile (the highest quartile). Additionally, HDL-C levels decreased as eGFR decreased. Pearson's correlation analysis revealed that HDL-C levels were associated with eGFR (r=0.16). After adjustment for some confounders, HDL-C was independently associated with all quartiles of eGFR in the participants. CONCLUSIONS: HDL-C was independently associated with kidney function in a community-dwelling general population. The association between low HDL-C levels and a decreased eGFR gradually strengthened as eGFR declined.

[Study on the relation between expression of angiotensin II receptor and apoptosis in myocardium in rats of endotoxemia].

OBJECTIVE: To analyze the expression of angiotensin II (ANG II) receptor and apoptosis in myocardium in rats of endotoxemia. METHODS: Model of endotoxemia was induced by intraperitoneal injection with lipopolysaccharide (LPS) 10 mg/kg in male Wistar rats and saline was injected into control group. The rats were killed at 2 h or 6 h after saline (control) or LPS . Expression of the correlation factors related to apoptosis of Bcl-2, Bax, AT1 and AT2 receptor in myocardial tissue were detected with immunohistochemistry (IHC), and changes of myocardial cells apoptosis was detected by the method of TUNEL. The gene expression of AT1 and AT2 receptor was examined by RT-PCR. The pathological changes of myocardial tissue were observed by electron microscope. RESULTS: Compared with control group , the expression of AT1 and AT2 receptor were significantly decreased, especially in 6 h group; and the expression of Bcl-2 and Bax were decreased, the ratio of Bcl-2/Bax had the downtrend as well as the apoptosis of myocardial cells. CONCLUSION: Interfered by LPS, the down regulation of AT1 and AT2 receptor expression has the negative relation with apoptosis of myocardial cells, this result indicated that down regulation of AT1 and AT2 receptor expression maybe related to cardiac functional impairment, which maybe help us to find a new protective path to prevent myocardial damage induced by systemic inflammatory.

Chronic kidney disease: an independent risk factor of all-cause mortality for elderly Chinese patients with chronic heart failure.

OBJECTIVE: To evaluate the prognostic value of chronic kidney disease (CKD) in elderly Chinese patients with chronic heart failure (CHF). METHODS: The study consisted of 327 elderly patients with CHF. All-cause mortality was chosen as an endpoint over the median follow-up period of 345 days. Cox regression analysis was used to identify the risk factors of mortality. RESULTS: The median age of the entire cohort was 85 years (60-100 years). The mortality for 168 elderly patients with CHF and CKD (51.4% of entire cohort) was 39.9% (67 deaths), which was higher than the mortality for CHF patients without CKD [25.2% (40/159 deaths)] and the mortality for entire cohort with CHF [32.7% (107/327 deaths)]. The Cox regression analysis showed that old age [hazard ratio (HR): 1.033; 95% confidence interval (95% CI): 1.004-1.064], CKD (HR: 1.705; 95% CI: 1.132-2.567), CHF New York Heart Association (NYHA) class IV (HR: 1.913; 95% CI: 1.284-2.851), acute myocardial infarction (AMI) (HR: 1.696; 95% CI: 1.036-2.777), elevated resting heart rate (HR: 1.021; 95% CI: 1.009-1.033), and decreased plasma albumin (HR: 0.883; 95% CI: 0.843-0.925) were independent risk factors of mortality for elderly patients with CHF. CONCLUSIONS: CKD was an independent risk factor of mortality for elderly Chinese patients with CHF.

Activation of anterior cingulate cortex produces inhibitory effects on noxious mechanical and electrical stimuli-evoked responses in rat spinal WDR neurons.

In present study, in vivo electrophysiological techniques were applied to examine the effects of anterior cingulate cortex (ACC) activation on mechanical and electrical stimuli-evoked responses in rat spinal cord wide-dynamic-range (WDR) neurons. We found that bilateral ACC electrical stimulation (100Hz, 20V, 20s) had different effects on neuronal responses to brush, pressure and pinch stimuli (10s). The brush-evoked neuronal responses at baseline, post 1min and post 5min were 60.8±15.0, 59.2±15.4 and 60.0±19.3 spikes/10s, respectively (n=10, P>0.05 vs. baseline). The pressure-evoked neuronal responses at baseline, post 1min and post 5min were 77.8±11.9, 38.0±7.8 and 45.8±7.6 spikes/10s, respectively (n=10, P<0.05 vs. baseline). The pinch-evoked neuronal responses at baseline, post 1min and post 5min were 137.6±16.7, 62.6±17.5 and 68.8±15.0 spikes/10s, respectively (n=10, P<0.05 vs. baseline). Furthermore, ACC stimulation generated distinct effects on the different components of wind-up response. The total numbers of late response (LR) and after-discharge (AD), but not early response (ER), significantly decreased. Collectively, the present study demonstrated that short-term ACC activation could generate long-term inhibitory effects on the responses of WDR neurons to noxious mechanical (pressure and pinch) and electrical stimuli. The results indicated that ACC activation could negatively regulate noxious information ascending from spinal cord with long-term effect, providing potential neuronal substrate for the modulation of ACC activation on nociception.

[Mesenchymal stem cells exist in the compact bones from four species of mammals].

The biological properties of cultured mesenchymal stem cells (MSC) have been intensively investigated, while there is still a paucity of information about the definite in vivo sites that harbor these stem cells due to the lack of specific surface markers. Previous data have demonstrated that human and murine MSC can be isolated from the compact bones. To investigate if it is the case for other species, the femurs from Wistar rats, Beagles, C57 mice and New Zealand rabbits were collected, minced and digested with collagenase type I. The digested bone fragments were seeded into the medium for human bone marrow culture after removal of the suspended cells in the digestion. The results showed that the fibroblast-like cells were observed to migrate from the bone fragments after several days of culture, and they gradually formed an adherent confluent layer. The adherent cells could be passaged and expressed homogenously the mesenchymal cell marker vimentin. Differentiation assays showed that these cells had the capacity to differentiate into osteoblasts and adipocytes. In conclusion, the results here provide new information for the further investigations on the in vivo biological features of MSC in the context of the simplicity of the compact bone structure.