Effect of Mast Cell Stabilizers in Hyperhomocysteinemia-induced Cardiac Hypertrophy in Rats

Singh, Amrit Pal; Singh, Manjeet; Balakumar, Pitchai

doi:10.1097/fjc.0b013e31817ae60f

Cited by 39 publications

(23 citation statements)

References 49 publications

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“…Five-micron-thick sections were stained with hematoxylin and eosin and Masson trichrome. The left ventricular wall thickness and cardiomyocyte diameter were measured as previously described [12] using an image analysis program (Image-Pro Plus 3.0). The diameters of at least 100 cardiomyocytes were determined in randomly selected visual fields at 400-fold magnification, and the mean cardiomyocyte diameter was expressed in micrometers.…”

Section: Biochemical Analysismentioning

confidence: 99%

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a “Western-style diet” by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels

Qin

et al. 2010

Acta Pharmacol Sin

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Aim:The examine the cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice (ApoE-/-mice) fed a "Western-style diet" and the effect of simvastatin intervention. Methods: Male ApoE-/-mice (n=36) were fed a "Western-style diet" from the age of 8 weeks. After 16 weeks, they were randomly given either simvastatin (25 mg·kg -1 ·d -1 ) or normal saline (control group) by gavage for 8, 16, or 24 weeks. The left ventricular (LV) wall thickness and diameter of the myocardial cells were determined with Hematoxylin-Eosin stain, and the level of fibrosis of the myocardial matrix was assessed with Masson stain. Real-time quantitative polymerase chain reaction and Western blotting analysis were used to determine the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9), Cathepsin S (Cat S), and the peroxisome proliferator-activated receptors (PPARs) in the myocardium of ApoE-/-mice. Results: ApoE-/-mice fed a "Western-style diet" showed an significant age-dependent increase in total cholesterol (TC), LV wall thickness, myocardial cell diameter and LV collagen content (P<0.05). The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05). Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05) . Conclusion: ApoE-/-mice fed a "Western-style diet" had cardiac hypertrophy and fibrosis, which worsened with age. Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

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Section: Biochemical Analysismentioning

confidence: 99%

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a “Western-style diet” by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels

Qin

et al. 2010

Acta Pharmacol Sin

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“…[42][43][44] Hem kli nik hem de prek li nik ça lış ma lar da, kar di yak hi per tro fi ile de hi per ho mo sis te i ne mi arasın da po zi tif bir iliş ki bu lun muş tur. 45,46 Hi per homo sis te i ne mi nin ne den ol du ğu ok si da tif stre sin MH'nin in fil tras yo nu ve bun la rın kol lajen sen te zinin in dük si yo nu ile kar di yak hi per tro fi ye ne den ol du ğu be lir til miş tir.…”

Section: Ye Ni̇ An Ti̇ Al Ler Ji̇k Mo Le Kül Le Ri̇n Kar Di̇ Yo Vas Kü Lerunclassified

The Role of Mast Cells in Cardiac Diseases and Surgery: Invited Commentary

Akgül¹,

Ünal²,

Kervan³

2011

Turkiye Klinikleri J Med Sci

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DAVETLİ YORUMÖ ÖZ ZE ET T Mast hücreleri, allerjik inflamatuar yanıtta etkili hücreler olarak bilinmektedir. Mast hücrelerinin histamin, triptaz, TNF-α, bFGF ve TGF-β gibi fibroblast fenotipi karakterinde ekstrasellüler matriks sentezi yapan mediyatörler ile özellikle fibrotik süreçte rol aldığı çalışmalar tarafından desteklenmektedir. Mast hücreleri ve diğer mediyatörleri, insan kalbini de içeren çeşitli hastalıklardan sorumlu tutulmuştur. Dilate kardiyomiyopatili insan kalbinde ve hayvan deneylerinde oluşturulmuş hipertansiyon, kalp krizi ve aortokaval fistül ile mitral regürjitasyona sekonder volüm yüklenmesinde mast hücre sayısında artış olduğu rapor edilmiştir. Aterosklerozun gelişimi özellikle granülosit, B ve T lenfositleri, mast hücreleri, dendritik hücreler ve progenitör hücreler gibi çeşitli tipteki immün sistem ile ilişkilidir. Koroner kan damarları çevresinde ve içinde mast hücrelerinin varlığı; kardiyak mast hücrelerinin aktivasyonu ve vazoaktif mediyatörlerin salınımı yoluyla iskemik kalp hastalığının patofizyolojisine katkıda bulunabileceğine işaret etmektedir. Bu çalışmada, mast hücrelerin kardiyak hastalıklardaki rolü incelenmeye çalışılmıştır. MAST HÜC RE LE Rİ hr lich 1878 yılında ani lin bo ya sı ile me tak ro ma tik bo ya nan ve da ha ön ce plaz ma hüc re le ri ola rak ta nım lan mış olan hüc re le rin fa go si toz yap tık la rı nı ve si top laz ma la rın da ki be lir gin gra nül le rin fa go si toz so-

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“…A standard curve was plotted using 5 50 mM of GSH and the results were expressed as micromoles of reduced glutathione per gram of wet tissue weight. 43,45) …”

Section: Estimation Of Tbarsmentioning

confidence: 99%

“…The concentration of TBARS value was expressed as nanomoles per gram of wet tissue weight. 42,43) Estimation of Superoxide Anion Generation…”

Section: Estimation Of Tbarsmentioning

confidence: 99%

“…Results were expressed as reduced NBT picomoles per minute per milligram of wet tissue. 43,44) Estimation of Reduced Glutathione The reduced form of glutathione (GSH) content in the heart was estimated using method of Beutler et al 45) The homogenate supernatant was mixed with trichloroacetic acid (10％ w/v) in a 1 : 1 ratio. The tubes were centrifuged at 1000 g for 10 min at 4°C.…”

Section: Estimation Of Tbarsmentioning

confidence: 99%

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Possible Role of JAK-2 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts

Singh¹,

Rohilla²,

Singh³

et al. 2009

YAKUGAKU ZASSHI

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The present study investigated the possible role of Janus kinase-2 (JAK-2) in hyperhomocysteinemia-induced attenuation of the cardioprotective eŠects of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated LangendorŠ's perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min, followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary eOEuent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid-reactive substances (TBARS), superoxide anion generation and the reduced form of glutathione. Ischemia-reperfusion (I/R) induced oxidative stress by increasing TBARS, superoxide anion generation and decreasing reduced form of glutathione in normal and hyperhomocystenemic rat hearts. Moreover, I/R produced myocardial injury, which was assessed in terms of the increase in myocardial infarct size, LDH and CK release in coronary eOEuent, and decrease in coronary ‰ow rate in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) aŠorded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of improvement in coronary ‰ow rate and reduction in myocardial infarct size, levels of LDH, CK, and oxidative stress. On the other hand, IPC-mediated myocardial protection against I/R-injury was abolished in hyperhomocysteinemic rat hearts. Tyrphostin AG490 (5 mM), a selective inhibitor of JAK-2, did not aŠect the cardioprotective eŠects of IPC in normal rat hearts, but its administration markedly restored the cardioprotective potential of IPC in hyperhomocysteinemic rat hearts. Administration of diazoxide (30 mM), an ATP-sensitive potassium (K ATP ) channel opener, also restored the cardioprotective eŠects of IPC in hyperhomocysteinemic rat hearts. In conclusion, it is suggested that the high degree of oxidative stress produced in hyperhomocysteinemic rat hearts during reperfusion and consequent activation of JAK-2 and closure of K ATP channels may be responsible for abolishing the cardioprotective potential of IPC against I/Rinduced myocardial injury.

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Effect of Mast Cell Stabilizers in Hyperhomocysteinemia-induced Cardiac Hypertrophy in Rats

Cited by 39 publications

References 49 publications

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a “Western-style diet” by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a “Western-style diet” by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels

The Role of Mast Cells in Cardiac Diseases and Surgery: Invited Commentary

Possible Role of JAK-2 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts

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