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ABSTRACT: Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear.
MI was produced in adult female Sprague-Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study.
T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to -4 expression was also observed in T4 treated MI rats.
These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.
Journal of Translational Medicine 01/2013; 11:40. · 3.41 Impact Factor
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ABSTRACT: Previous studies have shown gender differences in left ventricular remodeling after myocardial infarction. Results are varied, however, and reliable, comprehensive data for changes in cardiac myocyte shape are not available.
Young adult female and male Sprague-Dawley rats were used in this study and randomly assigned to the myocardial infarction and sham myocardial infarction groups. Myocardial infarction was produced by ligation of the left descending coronary artery. Four weeks after surgery, left ventricular echocardiography and hemodynamics were performed before isolating myocytes for size determination.
In general, left ventricular functional changes after myocardial infarction were comparable. Females developed slightly, but significantly, more left ventricular hypertrophy than males, and this was reflected by the relative increases in left ventricular myocyte volume. In both males and females, however, myocyte hypertrophy was due exclusively to lengthening of myocytes with no change in myocyte cross-sectional area.
This study demonstrates that post-myocardial infarction changes in LV function and myocyte remodeling are remarkably similar in young adult male and female rats.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 11/2010; 20(5):e189-95. · 1.63 Impact Factor
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ABSTRACT: In the crystal structure of the title compound, C(52)H(36)Br(4)O(12)S(8)·CH(2)Cl(2), the thia-calix[4]arene unit adopts a 1,3-alternate conformation with an intra-molecular C-H⋯O hydrogen bond and four C-H⋯π inter-actions, with the four 4-MeC(6)H(4)SO(3) groups located alternately above and below the virtual plane (R) defined by the four bridging S atoms. The benzene ring of each 4-MeC(6)H(4)SO(3) unit is nearly perpendicular to one of the two neighboring phenol rings with inter-planar angles varying from 72.97 (13) to 78.70 (13)°, while the dihedral angles between the plane (R) and the phenol rings range from 83.04 (7) to 84.30 (9)°. In the supra-molecular structure, a solvent-bridged dimer composed of two main mol-ecules is formed by four inter-molecular C-H⋯O hydrogen bonds and locally creates an R(4) (4)(26) motif. Such dimers associate further into chains by inter-dimer C-Cl⋯O short contacts [Cl⋯O 3.182 (5) Å]. Finally, these chains are linked into a two-dimensional network by a combination of inter-chain C-Br⋯O inter-actions [Br⋯O = 3.183 (3) and 2.966 (4) Å] as well as C-H⋯O hydrogen bonds.
Acta Crystallographica Section E Structure Reports Online 01/2010; 66(Pt 4):o871-2. · 0.35 Impact Factor
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ABSTRACT: It has been shown that hypothyroidism may lead to delayed wound healing after experimental myocardial infarction (MI) in rats and increased infarct size in dogs. However, the long-term effect of hypothyroidism on left ventricular (LV) remodeling after MI has not been determined. Adult female Sprague-Dawley rats with and without surgical thyroidectomy (TX) were used in the study. Four weeks after TX, MI or sham MI was performed on TX and non-TX rats. Rats from all groups were examined 4 wk later. Four weeks after TX, hypothyroid-induced LV dysfunction was confirmed by echocardiography. In terminal experiments 4 wk after MI, TX sham-MI rats showed smaller hearts and impaired LV function compared with non-TX sham-MI controls. TX + MI rats showed smaller hearts with bigger infarct areas, higher LV end-diastolic pressures, and greater impairment of relaxation (-dP/dt) compared with non-TX MI rats. Relative changes after MI between TX and non-TX rats for most other hemodynamic and echocardiographic indexes were similar. These results suggest that preexisting hypothyroidism exaggerates post-MI remodeling and worsens LV function, particularly diastolic function.
AJP Heart and Circulatory Physiology 11/2009; 298(1):H259-62. · 3.71 Impact Factor
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ABSTRACT: Thyroid hormone (TH) levels decline after a myocardial infarction (MI). Treatment with TH has been shown to improve left ventricular (LV) function in MI and other cardiovascular diseases, but the mechanisms are not clear. We have previously shown that TH can prevent myocyte apoptosis via Akt signaling in cultured neonatal rat cardiomyocytes. In this study, the effects of triiodo-L-thyronine (T3) on LV function and myocyte apoptosis after MI was examined in rats. After surgery, MI rats were treated with T3 for 3 days. Compared with sham-operated rats, MI rats showed significantly increased LV chamber dimension during systole and decreased LV function. T3 treatment increased LV +/-dP/dt but did not change LV chamber dimensions. MI rats also showed significantly increased myocyte apoptosis in the border area as assessed by DNA laddering and TUNEL assay. T3 treatment decreased the amount of DNA laddering, and reduced TUNEL positive myocytes in the border area, which was associated with phosphorylation of Akt at serine 473. These results suggest that T3 can protect myocytes against ischemia-induced apoptosis, which may be mediated by Akt signaling.
Journal of Molecular and Cellular Cardiology 02/2008; 44(1):180-7. · 5.17 Impact Factor
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ABSTRACT: A technique for isolation of cardiac myocytes and collection of whole heart tissue from individual hearts of adult rats is described in this study. After excision of the apical half of the left ventricle (LV) and cauterization of the cut edge, aortas were cannulated and high-quality isolated cardiac myocytes were collected after collagenase perfusion of the basal portion. Myocyte dimensions from the basal portion of cauterized and noncauterized hearts from matching rats were identical. Additionally, myocyte dimensions from the basal and apical halves of the LV were compared with the use of whole heart-isolated myocyte preps. No regional differences between basal and apical LV myocyte size were found. Therefore, this cauterization method can be used to collect isolated myocytes from the basal half and whole heart tissue from the apical half, with each half being representative of the other with respect to myocyte dimensions.
AJP Heart and Circulatory Physiology 10/2007; 293(3):H2004-6. · 3.71 Impact Factor
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Yue-Feng Chen,
Yue-Jin Yang,
Xi Chen,
Ying-Mao Ruan,
Rui-Cheng Sun,
Yi Tian,
Yan-Wen Zhou,
Qing-Zhi Wang,
Wen-Xue Si,
Ji-Lin Chen,
Run-Lin Gao,
Zai-Jia Chen
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ABSTRACT: To compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction (AMI) in rats.
AMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(-1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham operation group (group S, n = 27) was also established. Two subgroup (48 h subgroup and 4 weeks subgroup) was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry and Western blot analysis.
Compared with AMI control group, myocyte apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01) in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of bax and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and bax were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group (P < 0.05).
Both Atenolol and Metoprolol treatment can reduce cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 08/2006; 28(4):538-43.
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Yue-jin Yang, Yue-feng Chen,
Ying-mao Ruan,
Xi Chen,
Hui-dong Zhang,
Yi Tian,
Yan-wen Zhou,
Qing-zhi Wang,
Wen-xue Si,
Ji-lin Chen,
Run-lin Gao,
Zai-jia Chen
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ABSTRACT: To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction (AMI).
Eighty-three female SD rats underwent ligation of left anterior descending coronary artery, and were randomly assigned to 2 groups 24 hours later: carvedilol (n = 40, 10 mg.kg(-1).d(-1)was administered via direct gastric gavage 24 hs after the ligation, Group C) and AMI control group (n = 43, normal saline of the same volume was given by gastric gavage, Group MI). Another 27 rats were used as sham operation group (Group S, administered with normal saline too). The rats of each group were killed and their hearts were taken out 48 hours and 4 weeks after observation respectively (MI-48 h, MI-4 week, C-48 h, C-4 week, S-48 h, and S-4 week subgroups). TUNEL and DNA gel electrophoresis were used to detect the cardiomyocyte apoptosis. Immunohistochemistry and Western blotting were used to detect the expression of bcl-2 and bax.
The apoptotic indices of the infracted/scar, border and non-infarcted areas at any time-point of Group MI were all significantly higher than those of Group S (all P < 0.05). Only the apoptotic indices of the infracted/scar and border areas of the C-4 week subgroup were significantly lower than those of the MI-4 week subgroup (both P < 0.05), and were close to those of the non-infarcted area. DNA gel electrophoresis showed that the positive rate of Group S at any time-point were both 0, the positive rate of MI-48 h subgroup and C-48 h subgroup were both significantly higher than that of Group S (both P < 0.05) without significant difference between these 2 groups, and the positive rates of the MI-4 week subgroup and C-4 week subgroup were both 0. Immunohistochemistry showed that the bax gene expression was slightly to significantly increased in the infarcted/scar, border, and non-infarcted areas of the MI-48 h and MI-4 week subgroups. The bcl-2 expression was significantly increased only in the infracted area of the MI-48 h subgroup. The bcl-2 expression was slightly increased in the infracted and border areas of the C-48 h subgroup and the bax expression was significantly decreased in the infracted/scar area of the C-4 week subgroup. Western blotting showed that (1) the bcl-2 expression of the S-4 week subgroup was significantly higher than that of the S-48 h subgroup (P < 0.05), (2) the bcl-2 expression and bax expression of the MI-48 h subgroup were significantly higher than that of the S-48 h subgroup (P < 0.05 - 0.01), the bcl-2/bax ratio of the MI-48 h subgroup was significantly lower that that of the S-48 h subgroup, however, there were no significant differences in the bcl-2 and bax expression and bcl-2/bax ratio between the MI-4 week subgroup and S-48 h subgroup (all P > 0.05), and (3) There were no significant difference in the bcl-2 and bax expression between Group A and Group S (all P > 0.05), however, the bcl-2/bax ratios at the 2 time-points of Group C were both significantly higher than those of Group MI.
Cardiomyocyte apoptosis occurs in the infarction/scar, border and non-infarcted areas after AMI. Prolonged treatment with carvedilol reduces cardiomyocyte apoptosis in the scar and border areas and increases the expression ratio of bcl-2/bax.
Zhonghua yi xue za zhi 05/2006; 86(13):919-22.
