Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity. In this study, we examined whether activation of iNOS is responsible for palmitate-induced mitochondrial dysfunction, ER stress, and decreased adiponectin synthesis in 3T3L1 adipocytes. As expected, palmitate increased the expression levels of iNOS and ER stress response markers, and decreased mitochondrial contents. Treatment with iNOS inhibitor increased adiponectin synthesis and reversed the palmitate-induced ER stress response. However, the iNOS inhibitor did not affect the palmitate-induced decrease in mitochondrial contents. Chemicals that inhibit mitochondrial function increased iNOS expression and the ER stress response, whereas measures that increase mitochondrial biogenesis (rosiglitazone and adenoviral overexpression of nuclear respiratory factor-1) reversed them. Inhibition of mitochondrial biogenesis prevented the rosiglitazone-induced decrease in iNOS expression and increase in adiponectin synthesis. These results suggest that palmitate-induced mitochondrial dysfunction is the primary event that leads to iNOS induction, ER stress, and decreased adiponectin synthesis in cultured adipocytes.

Does The Mitral Annulus Shrink or Enlarge During Systole? A Real-Time 3D Echocardiography Study

This study was conducted to explore the geometrical changes of the mitral annulus during systole. The 3D shape of the mitral annulus was reconstructed in 13 normal subjects who had normal structure of the mitral apparatus using real-time 3D echocardiography (RT3DE) and 3D computer software. The two orthogonal (antero-posterior and commissure-commissure) dimensions, the areas (2D projected and 3D surface) and the non-planarity of the mitral annulus were estimated during early, mid and late systole. We demonstrated that the MA had a "saddle shape" appearance and it consistently enlarged mainly in the antero-posterior direction from early to late systole with lessening of its non-planarity, as was determined by 3D reconstruction using RT3DE and 3D computer software.

Assessment of Left Ventricular Function by Analysis of Volume-Time Curves of 16 Segments with Real-Time Three Dimensional Echocardiography : Left Ventricular Asynchrony as a Clinical Parameter for Patients with Heart Failure

BACKGROUND AND OBJECTIVES : Recent technical developments with high-resolution real-time 3-dimensional echocardiography (RT3DE) have facilitated the acquisition of high quality images and the analysis of segmental volume-time curves (VTCs). The purposes of this study were to assess left ventricular (LV) asynchrony with using the VTCs of 16 segments by RT3DE and to compare this with tissue Doppler imaging (TDI) as a clinical parameter. SUBJECTS AND METHODS : Twenty-three heart failure (HF) patients (LVEF: 25+/-6%, age: 60+/-13 years) and 16 normal controls underwent TDI and RT3DE at baseline and 1-year. The standard deviation (SD3) of the end systolic time to reach the minimal systolic volume for the 16 segments on VTCs was obtained by RT3DE. The standard deviation (SD2) of the electromechanical coupling time for the 8 segments was measured using TDI. RESULTS : SD3 was markedly higher in the HF patients than that in the controls (7.7+/-2.5 vs 1.5+/-1.0%, respectively, p<0.01) and it increased as the LVEF decreased (r=-0.85, p<0.01). SD2 was also significantly higher in the HF patients (27.0+/-8.6 vs 12.6+/-5.0 msec, respectively, p<0.01) and it had good negative correlation with the LVEF (r=-0.72, p<0.01). SD3 was well correlated with SD2 (r=0.66, p<0.01). At 1-year, the HF patients with an increased LVEF showed a decreased SD3 (7/13). In contrast, the patients with a decreased LVEF had an increased SD3 (3/13). CONCLUSION : The analysis of VTCs for the 16 LV segments with using RT3DE from a single acoustic window may be a useful clinical parameter for evaluating the LV function, including LV asynchrony, the LV volume and the LVEF.

Fractional transmural perfusion assessed by myocardial contrast echocardiography according to grades of collateral flow on coronary angiography / 대한내과학회지

BACKGROUND: A collateral flow can be assessed and graded by coronary angiography, however, the technique does not provide any information about perfusion. Myocardial contrast echocardiography (MCE) can assess collateral perfusion and has superior spatial resolution in defining its distribution. OBJECTIVE: To investigate the difference of transmural perfusion according to the angiographical collateral grade in normal myocardium, we performed MCE of collateral artery in 16 patients (m : f = 11 : 5, age: 57+/-13yrs.) with angina and compared the results with the angiographical grades. METHODS: In six patients with preexisting collaterals on baseline angiography, we performed MCE after intracoronary injection of sonicated Hexabrix. For 10 patients without preexisting collaterals on baseline angiography, we performed angiography, MCE for recruited collateral arteries during balloon inflation of stenotic coronary arteries (2 times for 120sec.). For 12 patients who underwent PTCA, we performed pressure wire simultaneously with angiography and MCE for recruited collateral arteries during balloon inflation. Fractional collateral flow(FCF) was defined by the ratio of coronary wedge pressure to proximal pressure(Pw/Pa). Angiographical collaterals were graded according to 'Rentrop' criteria(grade 0-3). Transmural thickness (TMT) and enhanced myocardial thickness (EMT) of an enhanced segment on MCE were measured at diastolic phase. The depth of collateral perfusion was estimated by collateral perfusion index (CPI) that was the ratio of EMT to TMT. RESULTS: There were significant differences of CPI with respect to angiographical grades according to one way ANOVA test (p< 0.05). One of five patients who had no recruited collaterals showed partial enhancement confined to the epicardium with CPI of 0.24. There was significant correlation between the angiographical grade and the CPI with Spearman's Rho value of 0.93(p< 0.0001). The angiographical grades were significantly correlated with FCF with the Spearman's Rho value of 0.87(p=0.0002). There was also significant correlation between FCF and CPI with Pearson's r=0.81 (p=0.0016). CONCLUSION: The higher the angiographical collateral grade is, the higher the collateral pressure and the deeper the fractional transmural perfusion from epicardium into endocardium gets.