Influence of phenotype conversion of epicardial adipocytes on the coronary atherosclerosis and its potential molecular mechanism.

OBJECTIVE: To investigate the phenotype conversion of epicardial adipocytes and its potential molecular mechanism during the occurrence and development of coronary atherosclerosis. METHODS: A total of 30 health male New Zealand white rabbits were used. In experiment group (n=15), rabbits were fed with high fat food to establish atherosclerosis animal model; rabbits in control group (n=15) were fed with normal food. RESULTS: At week 0, UCP-1 and PPARγ mRNA expressions in EAT and sBAT were significantly higher than in eWAT, and leptin mRNA expression lower than (P<0.05). In experiment group, the mRNA expressions of UCP-1 and PPARγ reduced gradually, but leptin mRNA increased progressively in EAT (P<0.05). UCP-1 expression reduced gradually, the newly generated blood vessels reduced significantly, but leptin and RAM11 increased gradually (P<0.05). The adipocyte volume in EAT increased gradually, but the adipocyte number reduced progressively (P<0.05). The number of mitochondria with multiple crests reduced gradually in EAT; IL-6 reduced the mRNA expressions of UCP-1 and PPARγ in adipocytes of BAT in a dose dependent manner, but it increased the mRNA expressions of leptin and STAT3 (P<0.05). In the presence of IL-6, JSI-124 increased the mRNA expressions of UCP-1 and PPAR-γ in adipocytes of BAT in a dose dependent manner, but it reduced the mRNA expressions of leptin and STAT3 (P<0.05). CONCLUSION: During the progression of atherosclerosis, there is a phenotype conversion of EAT from BAT to WAT, which further promotes the focal occurrence and development of atherosclerosis; IL-6 may activate JAK-STAT3 pathway to induce this conversion.

Associations of C1q/TNF-Related Protein-9 Levels in Serum and Epicardial Adipose Tissue with Coronary Atherosclerosis in Humans.

OBJECTIVE: To investigate the correlation of CTRP9 with coronary atherosclerosis. METHODS: Coronary angiography confirmed CAD in 241 patients (62 received CABG) and non-CAD in 121 (55 received valve replacement). RESULTS: Serum levels of LDL-C, CRP, TNF-α, IL-6, and leptin in CAD patients were significantly higher than those in non-CAD patients (P < 0.05), but APN and CTRP9 were lower (P < 0.05). Serum levels of CTRP9 and APN were negatively related to BMI, HOMA-IR, TNF-α, IL-6, and leptin but positively to HDL-C (P < 0.05) in CAD patients. After adjustment of APN, CTRP9 was still related to the above parameters. Serum CTRP9 was a protective factor of CAD (P < 0.05). When compared with non-CAD patients, leptin mRNA expression increased dramatically, while CTRP9 mRNA expression reduced markedly in epicardial adipose tissue of CAD patients (P < 0.05). The leptin expression and macrophage count in CAD group were significantly higher than in non-CAD group, but CAD patients had a markedly lower CTRP9 expression (P < 0.05). CONCLUSIONS: Circulating and coronary CTRP9 plays an important role in the inflammation and coronary atherosclerosis of CAD patients. Serum CTRP9 is an independent protective factor of CAD.

Reversible cardiogenic shock caused by atrioventricular junctional rhythm after percutaneous coronary intervention.

An 82-year-old female patient undergoing cardiogenic shock caused by atrioventricular junctional rhythm immediately after percutaneous coronary intervention (PCI) is described. Pharmacotherapy was invalid, and subsequent application of atrial pacing reversed the cardiogenic shock. PCI-related injury of sinuatrial nodal artery leading to acute atrial contractility loss, accompanied by atrioventricular junctional arrhythmia, was diagnosed. We recommend that preoperative risk evaluation be required for multi-risk patients. Likewise, emergent measures should to be established in advance. This case reminds us that atrial pacing can be an optimal management technique once cardiogenic shock has occurred.

[Impact of anti-OX-LDL antibodies on CD36 mRNA expression in monocytes].

AIM: To investigate the impact of antibodies to oxidized low-density lipoprotein (OX-LDL) on CD36 mRNA expression in monocytes and explore the mechanism underlying the impact on the formation of foam cells. METHODS: U937 cells and the monocytes of New Zealand rabbit were respectively cultured in vitro and divided into 4 groups: the control group (cultured in nutrient medium of RPMI1640), the OX-LDL group (with additional OX-LDL of 50 µg/L in nutrient medium), the OX-LDL+Ab-OX-LDL group (with additional OX-LDL of 50 µg/L and Ab-OX-LDL of 100 µg/L in nutrient medium) and the Ab-OX-LDL group (with additional Ab-OX-LDL of 100 µg/L in nutrient medium). After 24-hour culture, the expression of CD36 mRNA was detected by semi-quantitative RT-PCR. RESULTS: The expression of CD36 mRNA, either in the OX-LDL group or in the OX-LDL+Ab-OX-LDL group, was higher than that in the control group. After intervened by Ab-OX-LDL, the expression was respectively down-regulated by 64.80% in U937 cells and 35.18% in the monocytes of rabbit, which was statistically significant between the two species. CONCLUSION: Antibodies to OX-LDL could negatively regulate the expression of CD36 mRNA in monocytes, and prevent monocyte in taking OX-LDL through the pathway of antigen CD36.

[Membrane testosterone receptors in cultured vascular smooth muscle cells].

OBJECTIVE: To determine the presence of membrane testosterone receptors in cultured vascular smooth muscle cells (VSMC), and investigate their relationship with classical intracellular androgen receptors (iAR). METHODS: VSMCs were cultured from the thoracic aorta of male Sprague-Dawley rats by the explant method. Subconfluent VSMCs were incubated with serum-free medium for 24 h to obtain quiescent non-dividing cells, and then treated with the indicated agents. The aliquots of VSMCs were labeled with testosterone-BSA-FITC (T-BSA-FITC) and analyzed by flow cytometry. Classical iARs in intact- and permeabilized-cells were detected with anti-iAR antibodies and FITC-labeled secondary antibodies by immunofluorescence, followed by flow cytometry analysis. RESULTS: Incubation of VSMCs with T-BSA-FITC obviously increased their relative fluorescence intensity at 10 sec as compared with the untreated controls (P < 0.01), and so did it at 10 min in comparison with the treatment with BSA-FITC alone or together with free testosterone (P < 0.01). Pretreatment with iAR antagonist flutamide exhibited no significant influence on the relative fluorescence intensity of VSMCs (P = 0.318). Traditional iARs were not detectable on the surface of intact VSMCs, although permeabilized cells contained iARs. CONCLUSION: VSMCs contain testosterone receptors in the plasma membrane, and these membrane receptors are not identical to classical iARs.

[Testosterone at physiological level inhibits PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells].

OBJECTIVE: To explore the acute effects of testosterone at the physiological level on PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells (VSMCs). METHODS: VSMCs from the thoracic aorta of male Sprague-Dawley rats were cultured using the explant method. The subconfluent VSMCs were incubated with serum-free medium for 24 hours to obtain quiescent non-dividing cells and then treated with the indicated agents. For the measurement of [Ca2+]i, the VSMCs were loaded with fura-2. Changes of [Ca2+]i were determined ratiometrically with a Nikon TE-2000E system. RESULTS: The resting level of [Ca2+]i was around 100 nmol/L in the VSMCs. Exposing cells to perfusate containing 10 micromol/L PGF2alpha triggered an immediate and transient peak in [Ca2+]i, which gradually decreased afterwards. Interference at the peak with the physiological concentration (40 nmol/L) of testosterone significantly decreased the peak-to-baseline time of [Ca2+]i, compared with ethanol vehicle (104.9 +/- 27.0 s vs 153.5 +/- 40.4 s, P < 0.01). Pretreatment with testosterone at 40 nmol/L for 2 minutes also reduced the peak-to-baseline time of [Ca2+]i significantly in comparison with the ethanol control (120.6 +/- 32.0 s vs 151.4 +/- 27.4 s, P < 0.01), but it had no significant effect on the peak level of PGF2alpha-induced intracellular Ca2+ (390.0 +/- 126.0 nmol/L vs 403.4 +/- 160.7 nmol/L, P > 0.05). CONCLUSION: Testosterone at physiological concentration inhibits PGF2alpha-induced Ca2+ fluxes, probably via receptor-operated calcium channels by a non-genomic mechanism in VSMCs, which may be involved in the vasodilatory effect of testosterone.