Induction of myocardial PDCD4 in coronary microembolization-related cardiac dysfunction: evidence from a large-animal study.

BACKGROUND/AIMS: Coronary microembolization (CME) has been linked to myocardial inflammation and apoptosis. This study aims to investigate the role of the apoptotic protein PDCD4 in the myocardium after CME in minipigs. METHODS: Seventy Bama minipigs were randomized into four groups: control, CME, CME plus PDCD4-siRNA and CME plus control siRNA. CME was induced by injecting polyethylene microspheres into the left anterior descending artery. Cardiac function was evaluated. HE and HBFP staining were used to observe the degree of infarction. Western blotting and qPCR were used to evaluate the expression of PDCD4, TNF-α and caspase-3. The measurements were performed at 0, 3, 6, 9, 12 and 24 h after CME modeling in the CME and control groups. RESULTS: Cardiac function in the CME group was significantly decreased compared with the control group (P<0.05) and the expression of PDCD4 and TNF-α increased significantly (P<0.05). However, the infarct area did not differ between the CME and control groups at any time point (P>0.05). Furthermore, PDCD4-siRNA improved cardiac function and reduced PDCD4 and TNF-α expression compared with the CME plus control siRNA group at 9 h after modeling (P < 0.05), while the caspase-3 level was not different between the two groups. CONCLUSION: PDCD4 induction may be involved in CME-related cardiac dysfunction, and PDCD4 inhibition via siRNA may attenuate the cardiac impairment and be used as a treatment strategy for CME.

The involvement of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the regulation of inflammation following coronary microembolization.

BACKGROUND/AIMS: Growing evidence shows that phosphatase and tensin homolog deleted on chromosome ten (PTEN) is involved in regulating inflammation in different pathological conditions. Therefore, we hypothesized that the upregulation of PTEN correlates with the impairment of cardiac function in swine following coronary microembolization (CME). METHODS: To possibly disclose an anti-inflammatory effect of PTEN, we induced swine CME by injecting inertia plastic microspheres (42 µm in diameter) into the left anterior descending coronary artery and analyzed the myocardial tissue by immunochemistry, qRT-PCR and western blot analyses. In addition, we downregulated PTEN using siRNA. RESULTS: Following CME, PTEN mRNA and protein levels were elevated as early as 3 h, peaked at 12 h, and then continuously decreased at 24 h and 48 h but remained elevated. Through linear correlation analysis, the PTEN protein level positively correlated with cTnI and TNF-α but was negatively correlated with LVEF. Furthermore, PTEN siRNA reduced the microinfarct volume, improved cardiac function (LVEF), reduced the release of cTnI, and suppressed PTEN and TNF-α protein expression. CONCLUSION: This study demonstrated, for the first time, that PTEN is involved in CME-induced inflammatory injury. The data generated from this study provide a rationale for the development of PTEN-based anti-inflammatory strategies.

Anomalous origin of left anterior descending and circumflex coronary artery from two separate ostia in the right sinus of valsalva with unusual dominant right coronary artery.

Anomalous origin of left anterior descending (LAD) and left circumflex (LCX) coronary artery from two separate ostia in the right sinus of Valsalva (RSOV) with unusual dominant right coronary artery is an exceedingly rare congenital coronary anomaly. We report a case of a 69-year old woman who was admitted to the hospital because of atypical chest pain. Both multislice computed tomography and coronary angiography revealed this kind of anomaly. Since the benign anomaly and the absence of definite ischemia, the patient doesn't need any specific therapy for this anomaly and is required regular follow-up.

[Short- and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy].

OBJECTIVE: To evaluate the short-term, and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy (DCM). METHODS: Sprague-Dawley rats were administered adriamycin intraperitoneally to develop DCM. Grouping of rats: Group A contained normal rats, and Group B contained DCM rats. Both Group A and B were not given drug treatment. Group C and D contained DCM rats, however, Group C was administered perindopril 2mg/(kg x d) while Group D was administered perindopril 1mg/(kg x d) and irbesartan 25mg/(kg x d). Brain natriuretic peptide (BNP) was determined by enzyme linked immunosorbent assay; plasma potassium and creatinine were measured; the pathological lesions of cardiac muscle tissues were evaluated after HE staining; and the survival time of each rat during the intervention was recorded. RESULTS: After the three-week intervention, the plasma concentrations of BNP in Group D were lower than those in Group C (P<0.05). In each group, plasma concentrations of potassium and creatinine showed no significant differences between pre-intervention and post-intervention (P>0.05); pathological lesions of cardiac muscle tissues in both Group C and D were attenuated compared with those in Group B (P<0.01), but pathological lesions of cardiac muscle tissues showed no significant differences between Group C and Group D (P>0.05). Log-rank test showed that the life span of Group C was shorter than that of Group D (P<0.05); Cox regression analysis showed that both combination therapy and monotherapy with perindopril could prolong the survival time, but the effect of combination therapy was more obvious. CONCLUSION: Combination therapy with perindopril and irbesartan in a rat model of DCM can more effectively improve the cardiac function and long-term prognosis than those monotherapy with perindopril. Both these two treatment plans can attenuate the pathological lesions of cardiac muscle tissues, without elevating the concentrations of plasma potassium and creatinine.

[Relevant factors of microalbuminuria in aged patients with essential hypertension].

OBJECTIVE: To investigate the relationship between microalbuminuria and endothelial-dependent relaxing function and atherosclerosis of common carotid artery (CCA) in aged patients with essential hypertension (EH). METHODS: Sixty-four aged EH patients were recruited. According to the albumin excretion rate (AER) in the urine measured by immunoturbidimetry, patients were divided into 2 groups: normoalbuminuria group (NAU group) and microalbuminuria group (MAU group). Thirty aged persons without EH were served as the control group. The endothelium-dependent relaxing function of blood vessels, intima-media thickness (IMT) and the plaque of CCA were measured by color Doppler ultrasound. RESULTS: The flow-mediated dilation in the MAU group [(4.98+/-1.35)%] and that in the NAU group [(6.31+/-1.14)%] were significantly lower than that in the control group [(9.09+/-1.83)%, P<0.05, respectively], especially lower in the MAU group. The IMT of CCA in the MAU group [(0.97+/-0.19)mm] and that in the NAU group [(0.86+/-0.10)mm] were significantly thicker than that in the control group [(0.78+/-0.13)mm] (P<0.05, respectively), especially thicker in the MAU group. The analysis of multiple stepwise regression showed that the microalbuminuria was successively related to EDF, the IMT of CCA, the plaque index of CCA, systolic blood pressure, etc. CONCLUSION: EDF is impaired, and there is the atherosclerosis of CCA in aged patients with EH. Microalbuminuria correlates with the decrease of endothelium-dependent relaxing function and the IMT of CCA in aged patients with EH.