Effect of moxonidine hydrochloride on left ventricular hypertrophy in spontaneously hypertensive rats

AIM:To investate the effect of domestric moxonidine hydrochloride on myocardium fibrosis and coronary artery microvascular structure in left ventricular hypertrophy of spontaneously hypertensive rats(SHR).METHODS:30 male SHR, aged 20 weeks, were divided into group Mox+SHR, Cap+SHR and SHR randomly (10 in each group). 10 age and sex-mached sprauge-dawley rats were designed as normal control(NC). At the end of 13 weeks, left ventricular wight/body weight ratio(LVW/BW), collagen volume fraction(CVF) and standardized perivascular collagen area(PVCA) as well as intramyocardial arterial average medial thickness (AMT) were determined.RESULTS:LVW/BW, CVF, PVCA and AMT in group Mox+SHR were lower significantly than that in group SHR, respectively.CONCLUSION:Long-term antihypertensive treatment with moxonidine hydrochloride reduces myocardium fibrosis and improves impaired coronary artery microvascular structure in left ventricular hypertrophy.     

Expression of cathepsin C and tumor necrosis factor-α in human coronary artery and their relationships with coronary heart disease

AIM To explore the possible mechanism of cathepsin C （CTSC） and tumor necrosis factor-α （TNF-α） in coronary heart disease （CHD） by detecting the protein expression of CTSC and TNF-α in human coronary artery tissue. METHODS The coronary artery tissues from 52 cases of CHD and 25 cases of accidental death without any heart disease in the Forensic Judicial Expertise Center of Guizhou Medical University from October 2018 to December 2019 were collected as CHD group and control group, respectively. The coronary artery stenosis and intimal plaque formation were examined by histopathology, the protein expression of CTSC and TNF-α was determined by Western blot, and the intracellular expression of CTSC and TNF-α was analyzed by immunohistochemical staining. RESULTS The results of HE staining showed that the intima of coronary artery in control group was smooth, and no thickening or stenosis was observed. In CHD group, the intima thickened irregularly, atherosclerotic plaques formed, the intima became thinner and the lumen showed eccentric stenosis in varying degrees （P<0.05）. The results of Western blot showed that the expression of CTSC and TNF-α in CHD group was significantly higher than that in control group （P<0.05）. Immunohistochemical staining showed that both CTSC and TNF-α were expressed in the cytoplasm of foam cells, and their positive expression was significantly higher than that in control group （P<0.05）. The results of Pearson moment correlation analysis showed that there was positive correlation between the expression of CTSC and TNF-α in CHD （r²=0.743, P<0.05）. CONCLUSION The up-regulated expression of CTSC in coronary artery tissue may promote the expression of TNF-α and affect the occurrence and development of CHD.     

Captopril exerts myocardial protective effect in coronary microembolization rats by inhibiting oxidative stress injury and alleviating inflammatory response

AIM: To investigate the effects of captopril (CAP) on oxidative stress injury and inflammatory response induced by coronary microembolization (CME) and its related molecular mechanisms. METHODS: The rat model of CME was established by clamping the rat artery and injecting blood microemboli. The rats were divided into control group, CME group and CME+CAP group, with 6 rats in each group. The myocardial tissues of each group were collected. The changes of myocardial structure and the degree of inflammatory response were analyzed by HE staining. Cardiomyocyte apoptosis was detected by TUNEL staining. The fluorescence intensity of cleaved caspase-3 was detected by immunofluorescence obervation. The protein levels of cleaved caspase-3 and Bax were determined by Western blot. The activity of superoxide dismutase (SOD) and catalase was measured by ELISA. The production of reactive oxygen species (ROS) was detected by DHE fluorescence staining. RESULTS: CAP significantly reduced the myocardial structural changes (P<0.05), inflammatory cell infiltration (P<0.01), number of apoptotic cardiomyocytes (P<0.01), the protein levels of cleaved caspase-3 and Bax (P<0.01), and ROS production levels (P<0.01), but promoted the activity of antioxidant markers SOD and catalase (P<0.01) in the CME rats.CONCLUSION: CAP attenuates CME-induced myocardial injury by resisting oxidative stress and alleviating inflammatory response.     

Mechanism of quercetin improving rat coronary artery myogenic response under high glucose

AIM: To investigate the mechanism of quercetin improving rat coronary artery myogenic response under high glucose (HG) by measuring muscle tension of coronary arterial ring and recording voltage-gated K⁺ channel (Kv) current of coronary artery smooth muscle cells by whole cell patch clamp. METHODS: The coronary rings from the normal SD rats were acutely isolated, and then divided into 6 groups: (1) control group; (2) HG group; (3) HG+low dose (3 μmol/L) of quercetin group; (4) HG+moderate dose (10 μmol/L) of quercetin group; (5) HG+high dose (30 μmol/L) of quercetin group; (6) HG+C6303 (PKC inhibitor)+high dose of quercetin group. Determinations of coronary artery response to vasoconstrictor (60 mmol/L KCl or 0.1 mmol/L U46619) or vasodilator (ACh at 10^-9~10^-5 mol/L) were performed, and the percentage of coronary ring tension was calculated using the contraction as 100% caused by 60 mmol/L KCl. The rat coronary artery smooth muscle cells were acutely isolated for recording the Kv current using whole cell patch clamp. RESULTS: Compared with control group, the contraction amplitudes to 60 mmol/L KCl or 0.1 mmol/L U46619 were significantly increased under HG incubation. Quercetin intervention concentration-dependently reduced the coronary artery contraction amplitude. Incubation of PKC specific inhibitor C6303 attenuated the effect of quercetin. Compared with control group, the diastolic amplitude to ACh decreased significantly in HG group, and quercetin intervention concentration-dependently increased the coronary artery diastolic amplitude. Incubation of PKC specific inhibitor C6303 attenuated the effect of quercetin. Compared with control group, HG incubation inhibited Kv current of coronary artery vascular smooth muscle cells significantly, and quercetin intervention attenuated the inhibitory effect of HG on Kv current intensity. Incubation of PKC specific inhibitor C6303 attenuated the effect of quercetin. CONCLUSION: Quercetin has a protective effect on myogenic response of coronary artery under HG and the effects is related to the increase in Kv current and the activation of PKC in vascular smooth muscle cells.     

Model construction of rat coronary artery smooth muscle cell endoplasmic reticulum stress induced by thapsigargin

AIM: To investigate the primary culture method for coronary artery smooth muscle cells (CASMCs), and to establish the endoplasmic reticulum stress (ERS) model in CASMCs of SD rats. METHODS: CASMCs were cultured by tissue explant method. The morphological characteristics were observed under optical microscope. The marker proteins of CASMCs, including α-SMA and SM-MHC, were identified by immunofluorescence technique. The protein expression levels of BiP and CHOP, the marker molecules of ERS, were determined by Western blot. RESULTS: The spindle-shaped CASMCs climbed out from the edge of coronary artery tissues after 6 d, and formed the typical "hill and valley" growth pattern of CASMCs at 9~10 d. The result of immunofluorescence technique showed that α-SMA and SM-MHC were positively expressed. The results of Western blot showed that the protein expression of BiP and CHOP in TG (1 and 2 μmol/L) treatment groups was increased compared with control group. Compared with control group, the protein expression of BiP and CHOP was significantly increased after 1 μmol/L TG treatment for 24 and 48 h. CONCLUSION: CASMCs can be successfully cultured by tissue explant method. ERS model of CASMCs was established by 1 μmol/L TG treatment for 24 h.     

Myocardial dysfunction resulting from coronary microembolization

Coronary microembolization is a significant and frequent complication of primary percutaneous coronary intervention in the patients with acute myocardial infarction. More importantly, coronary microembolization is a main reason of dysfunction of microcirculation. The mechanism of myocardial disfunction resulting from coronary microembolition was associated with the vascular active materials released from platelet, platelet aggregation, which aggravate microembolization in microcirculation, endothelial dysfunction and inflammation.     

Serum concentration of S100-B protein in patients during CABG with or without cardiopulmonary bypass

AIM: To investigate the mutative law of the serum S100-B protein in patients undergone coronary artery bypass grafting with or without cardiopulmonary bypass (CPB-CABG or non-CPB CABG), and to compare the degree of cerebral injury in patients during CABG between the two different surgical manipulations.METHODS: 30 patients were divided into two groups: CPB-CABG group (group A) and non-CPB CABG group (group B). Every group included 15 patients. Blood from jugular vein was phlebotomized in every patients at the following 8 time points: before operation (OP), after anaesthesia, end of grafting, end of OP, 2 h after OP, 6 h after OP, 12 h after OP and 24 h after OP. The serum concentrations of S100-B protein in the samples were measured.RESULTS: The level of serum S100-B protein increased markedly at the beginning of CABG, and the peak value of group A (2.32 μg/L±0.26 μg/L) was treble higher than that in the patients in group B (0.71 μg/L±0.14 μg/L). The levels of S100-B protein tend to normal level in both groups 24 h after OP. The level of S100-B protein had notable relation with the time of CABG in group A and the manipulative time on the heart in group B.CONCLUSION: The degree of cerebral damage can be valued by investigating the mutative law of the serum S100-B protein in patients undergone CPB-CABG and non-CPB CABG. The non-CPB CABG reduces the degree of cerebral damage and avoids the functional disorder of central nerve.     

Potassium antagonizes damage of coronary artery induced by high salt intake

AIM：To investigate the effect of potassium treatment on coronary arterial impairment induced by high salt intake. METHODS：Sprague-Dawley rats (4-week-old, n=10 in each group) received distilled water (NS), water containing 1.5% NaCl (HS), or 1.5% NaCl and 0.5% KCl (HS+HP) for 16 weeks. Systolic blood pressure (SBP) was determined by tail plethysmography every 2 weeks. After 16 weeks of treatment, vascular remodeling, superoxide production, malondialdehyde (MDA) content, and endothelial nitric oxide synthase (eNOS) and gp91 expression in the coronary arteries were detected. RESULTS：After 16 weeks of salt loading, the rats in HS group was divided into salt sensitive subgroup and salt resistance subgroup according to the tail-cuff blood pressure. In this experiment, the salt-sensitive rats were selected as HS group. In HS group, salt loading significantly increased SBP, serum MDA and gp91 expression, decreased serum NO and eNOS expression in the coronary arteries, and induced the coronary artery remodeling compared with NS group. In salt-loaded SD rats, 16-week potassium treatment abrogated the effects induced by salt loading. CONCLUSION：High salt may affect structural and functional changes in coronary arteries by activating oxidative stress. Potassium treatment antagonizes the effect of high salt intake.     

Changes in plasma neurotension level of patients with coronary heart disease and its clinical significance

AIM: To investigate the plasma neurotensin(NT) concentration in patients with coronary heart disease: acute myocardial infarction(AMI),unstable angina(UA),stable angina pectoris(SAP), old myocardial infarction (OMI), and to study the relationship between the plasma NT level and the myocardial ischemia . METHODS:The plasma NT concentration of 30 patients with AMI,32 pat ients with UA,35 patients with SAP,31 pat ients with OMI and 32 normal controls were determined by radioimmunoassay(RIA). RESULTS: The plasma NT level in patients with AMI(24 h),in patients with UA when angina attacked is significantly higher than that of healthy controls. The plasma NT level in patients with SAP, in patients with OMI is not significantly different from that of healthy controls. The NT level of patients with UA when angina attacked is significantly higher than that after 2 weeks treatment (P＜0.01). The NT level of AMI patients rose from early period and reached peak value at 24 h .It began to decline at 48h,and restored to normal level at 72h. CONCLUSION: When acute myocardial ischemia occured in patients with coronary heart disease, the plasma NT level was elevated. This suggests NT may have participated in the pathophysiological course of myocardial ischemia.     

Rheological properties and hemoglobin structure of red blood cells in cri-tically ill patients with coronary heart disease

AIM: To study the rheological properties of red blood cells (RBC) and the structure of hemoglobin in critically ill patients with coronary heart disease. METHODS: At pH 7.4, the rheological properties of RBC and the structure of hemoglobin isolated from critically ill patients with coronary heart disease and from healthy people were studied with both static and dynamic imaging techniques and ultraviolet-visible spectroscopy. RESULTS: The rheological properties of RBC from the critically ill patients with coronary heart disease were significantly different from those of healthy people. The bending modulus, which indicates the rigidity of RBC, was greater in the patients than that in healthy people. The absorption spectra of the hemoglobin of critically ill patients with coronary heart disease were almost the same as those of healthy people. CONCLUSION: The morphology and flexibility of RBC in critically ill patients with coronary heart disease are worse than those in healthy people, whereas the structure of hemoglobin in the patients is basically found no difference from that in healthy people.