Urotensin II promotes aldosterone expression in rat aortic adventitial fibroblasts.

Urotensin II (UII) contributes to cardiovascular diseases by activating vasoactive peptides. The present study aimed to determine the effect of UII on aldosterone (ALD) and its receptor in cultured adventitial fibroblasts (AFs) and the tunica adventitia of rat vessels to explore the possible mechanisms underlying vascular remodeling. Expression levels of aldosterone and its receptor on tunica adventitia were determined using immunohistochemistry. Growth­arrested AFs and tunica adventitia from rat vessels were incubated with UII and inhibitors of various signal transduction pathways. ALD receptor (ALD­R) mRNA expression levels and ALD protein exoression levels were determined by reverse transcription­quantitative polymerase chain reaction and ELISA, respectively. Aldosterone and its receptors were expressed on tunica adventitia. UII promoted ALD protein secretion from cells in a dose­ and time­dependent manner. ALD­R mRNA expression in cells was also dysregulated. Furthermore, the effects of UII were substantially inhibited by treatment with the inhibitors PD98059, Y­27632, H­7, CSA and nicardipine. These results were further verified in the tunica adventitia of rat vessels. The present findings indicated that UII stimulated ALD protein secretion and ALD­R mRNA expression in AFs and in the tunica adventitia of rat vessels; moreover, this effect may be mediated by signal transduction pathways involving MAPK, Rho, PKC, calcineurin and Ca2+. UII may also contribute to vascular remodeling by stimulating the production of ALD and its receptor.

Electrocardiographic characteristics in angiographically documented occlusion of the dominant left circumflex artery with acute inferior myocardial infarction: limitations of ST elevation III/II ratio and ST deviation in lateral limb leads.

BACKGROUND: The prognosis of dominant left circumflex artery (LCx) occlusion-related inferior acute myocardial infarction (AMI) patients is poor, but the electrocardiographic (ECG) characteristics of this AMI entity have not been described. METHODS: One hundred thirty-five patients with first dominant right coronary artery (RCA) or dominant LCx-related inferior AMI were included. The characteristics of ECG obtained on admission for 55 patients with culprit lesions proximal to the first major right ventricular (RV) branch of dominant RCA (group proximal dominant RCA), 62 patients with culprit lesions distal to the first major RV branch of dominant RCA (group distal dominant RCA), and 18 patients with culprit lesions in dominant LCx (group dominant LCx) were compared. RESULTS: There were no significant differences among the 3 groups in the prevalence regarding an S/R ratio greater than 1:3 in aVL, ST elevation in aVR (ST upward arrow(aVR)), ST depression in aVR (ST downward arrow(aVR)) of 1 mm or more, and atrioventricular block. Greater ST elevation in lead III than in II and greater ST depression in aVL than I showed specificity of 17% and 44% to identify dominant RCA as culprit lesion, respectively. All 3 groups could be distinguished on the basis of ST upward arrow(V4R), ST downward arrow(V4R), ST downward arrow(V3)/ST upward arrow(III) of 1.2 or less, and ST downward arrow(V3)/ST upward arrow(III) of more than 1.2. CONCLUSIONS: Greater ST elevation in lead III than in II, greater ST depression in aVL than I, and an S/R ratio of greater than 1:3 in aVL were not useful to discriminate between dominant RCA and dominant LCx occlusion-related inferior AMI. ST-segment deviation in lead V(4)R and the ratio of ST downward arrow(V3)/ST upward arrow(III) were useful in predicting the dominant artery occlusion-related inferior AMI.

In rats with myocardial infarction, interference by simvastatin with the TLR4 signal pathway attenuates ventricular remodelling.

OBJECTIVE: The objective of this study was to investigate the effect of simvastatin on TLR4,TNF-alpha and IL-6 expression in the myocardium and its relation to left ventricular (LV) remodelling in a rat model of myocardial infarction (MI) and to investigate the mechanism by which simvastatin improves LV remodelling in rats after MI. METHODS AND RESULTS: The rat MI models were established by ligation of the left anterior descending coronary artery and divided into three groups: (I) an untreated MI group; (2) a group treated with simvastatin [40 mg/(kg/d)] for 4 weeks; (3) the sham group. Cardiac geometry and function were determined by echocardiography and infarct size was determined by the histomorphometric analysis; the expression ofTLR4 in the myocardium was measured by RT-PCR and western blotting;TNF-alpha and IL-6 levels in myocardial homogenate and serum were measured by ELISA. LVEDD and LVESD significantly increased and fractional shortening (FS) markedly decreased in the MI group. It was clear that simvastatin inhibited LV dilation and improved LV function after MI without affecting infarct size. The expression of TLR4, TNF-alpha and IL-6 in the myocardium significantly increased in the MI group and simvastatin markedly inhibits the expression of TLR4, TNF-alpha, and IL-6 in the myocardium after MI. Serum TNF-alpha and IL-6 levels between the MI group and the simvastatin group remained unchanged. Both in the MI group and the simvastatin group,TLR4 protein positively related to LVEDD and to the levels of TNF-alpha and IL-6 in the myocardium, respectively. CONCLUSION: Amelioration of LV remodelling in rats after MI by simvastatin might be associated with its effect on the TLR4-mediated signalling pathway in the myocardium.