ABSTRACT
This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism.A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups at random:ND group (n=10) and HD group (n=10),in which the rats were given a normal chow diet or a high-fat diet for 20 weeks following a one-week adaptation; ND+telmisartan (n=10) group and HD+telmisartan group (n=10),in which the rats were initially administered in the same way as the ND or HD group,and then they were orally gavaged with telmisartan (5 mg/kg daily)additionally for 5 weeks.Related inflammatory factors were measured by ELISA.Monocyte chemotactic protein 1 (MCP-1),phosphorylated JNK and Iκ B-α expressions in both adipose and liver were detected by Western blotting.CRP and angiotensin Ⅱ receptor 1 (AT1) mRNA expressions in both adipose and liver were determined by RT-PCR.The results showed that telmisartan administration in vivo reversed insulin resistance as evidenced by a decrease in plasma fasting glucose levels,plasma fasting insulin levels and homeostasis model of assessment-insulin resistance (HOMA-IR).Furthermore,telmisartan administration significantly reduced serum CRP,TNF-α and IL-1β levels,and elevated serum IL-10 levels.It was also found to hamper the high-fat diet-induced increase in CRP mRNA,AT1 mRNA and MCP-1,and decrease in Iκ B-α in both adipose and liver.It was concluded that telmisartan administration in vivo may improve insulin resistance through attenuated inflammatory response pathways.
ABSTRACT
Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease. However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known. To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic). Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period. Using the arbitrary cutoff for tHcy (＜18 μrnol/L and ≥18 μtmol/L) and hsCRP (＜1 mg/L, 1-3 mg/L and ＞3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P＜0.01). The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18μmol/L) and hsCRP (＞3 mg/L) compared with those with low tHcy (＜18 μmol/L) and hsCRP (＜1 mg/L). The increased tHcy level (≥18 μ mol/L) combined with increased hsCRP level (＞3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion. The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone. Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.
ABSTRACT
This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy. A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited. IL-6 level was detected by using enzyme linked immunosorbent assay. Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay. The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects. Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036). The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030). After adjusting for other factors,cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488). It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF. Elevated cystatin C level is also indicative of the increased risk of AF.
ABSTRACT
Tubulointerstitial fibrosis(TIF)is a common pathological feature of end-stage kidney disease.Previous studies showed that upregulation of TGFβ1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction.This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFβ1 in the rodent model of chronic renal failure involving 5/6 nephrectomy.The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model.Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group,but the lesion was attenuated mostly in irbesartan-treated group.Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFβ1 which was up-regulated in operation groups.Western blot showed that irbesartan treatment down-regulated the expression of TGFβ1,phosphorylated smad2(p-smad2),AT1R and phosphorylated p38(p-p38)MAPK,but significantly up-regulated the protein expression of smad6 as compared with operation group.These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6,TGF-β1,p-smad2,AT1 and p-p38 MAPK.
ABSTRACT
Dizziness,chest discomfort,chest depression and dyspnea are a group of symptoms that are common complaints in clinical practice. Patients with these symptoms are usually informed that while neurosis consequent to coronary heart disease is excluded nonetheless they remain unhealthy with no rational explanation or treatment. 165 cases of these symptoms and 85 control subjects were reviewed and underwent further medical history inquiry,routine EKG test and cardiac ultrasound examination. Thirty-five patients received coronary artery angiography to exclude coronary heart disease. Serum myocardial autoantibodies against beta1-adrenoceptor,alpha-myosin heavy chain,M2-muscarinie receptor and adenine-nucleotide translocator were tested,and inflammatory cytokines and high sensitivity C-reaction protein were measured and lymphocyte subclass was assayed by flow cytometry. All patients had a complex of four symptoms or tetralogy: (1) persistent throat or upper respiratory tract infection,(2) neck pain,(3) chest pain and (4) chest depression or dyspnea,some of them with anxiety. Anti-myocardial autoantibodies (AMCAs) were present in all patients vs. 8% in and CD4-CD8+ lymphocytes were significantly higher and CD56+ lymphocytes lower in patients than those in controls (P<0.01). The ratio of serum pathogen antibodies positive against Coxsackie virus-B,cytomegalovirus,Mycoplasma pneumoniae and Chlamydia pneumoniae were all markedly higher in patients. These data led to identification of a persistent respiratory infection-related clinical syndrome,including persistent throat infection,neck spinal lesion,fib cartilage inflammation,symptoms of car-diac depression and dyspnea with or without anxiety.
ABSTRACT
. These results suggest that simvastatin could stimulate the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.