scholarly journals Angiotensin II Facilitates Matrix Metalloproteinase-9-Mediated Myosin Light Chain Kinase Degradation in Pressure Overload-Induced Cardiac Hypertrophy

2017 ◽  
Vol 44 (6) ◽  
pp. 2281-2295 ◽  
Author(s):  
Shun Wang ◽  
Mian Cheng ◽  
Zhengqing Hu ◽  
Shan Hu ◽  
Qiang Zou ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Matrix Metalloproteinase ◽  
Cardiac Hypertrophy ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Pressure Overload ◽  
Ang Ii ◽  
Myosin Light Chain 2 ◽  
Metalloproteinase 9

Background/Aims: Angiotensin II (Ang II) has been shown to promote cardiac remodeling during the process of hypertrophy. Myosin light chain kinase (MLCK), a specific kinase for the phosphorylation of myosin light chain 2 (MLC2), plays an important role in regulating cardiac muscle contraction and hypertrophy. However, whether Ang II could facilitate cardiac hypertrophy by altering the expression of MLCK remains unclear. This study aimed to investigate this effect and the underlying mechanisms. Methods: Cardiac hypertrophy was induced via pressure overload in rats, which were then evaluated via histological and biochemical measurements and echocardiography. Angiotensin-converting enzyme inhibitor (ACEI) was used to inhibit Ang II. Neonatal rat cardiomyocytes were stimulated with Ang II to induce hypertrophy and were treated with a matrix metalloproteinase 9 (MMP9) inhibitor. Myocyte hypertrophy was evaluated using immunofluorescence and qRT-PCR. Degradation of recombinant human MLCK by recombinant human MMP9 was tested using a cleavage assay. The expression levels of MLCK, MLC2, phospho-myosin light chain 2 (p-MLC2), myosin phosphatase 2 (MYPT2), and calmodulin (CaM) were measured using western blotting. Results: ACEI improved cardiac function and remodeling and increased the levels of MLCK and p-MLC2 as well as reduced the expression of MMP9 in pressure overload-induced cardiac hypertrophy. Moreover, the MMP9 inhibitor alleviated myocyte hypertrophy and upregulated the levels of MLCK and p-MLC2 in Ang II-induced cardiomyocyte hypertrophy. Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. Conclusion: Our results suggest that Ang II is involved in the degradation of MLCK in pressure overload-induced cardiac hypertrophy and that this process was mediated by MMP9.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

Abstract 1102: Cardiac-Specific Myosin Light Chain Kinase (MLCK), a Third Member of MLCK Family, Potentiates Sarcomere Formation and Cardiac Contraction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jason Y Chan ◽  
Morihiko Takeda ◽  
Laura E Briggs ◽  
Jonathan T Lu ◽  
Nobuo Horikoshi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Cardiac Hypertrophy ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Contractile Function ◽  
Severe Heart Failure ◽  
Cardiac Contraction

Background: Two myosin light chain kinase (MLCK) proteins, skeletal (encoded by mylk2 gene) and smooth muscle MLCK (encoded by mylk1 gene) have been shown to be expressed in mammals. Human mylk2 has been mapped as a disease locus for familial cardiac hypertrophy (OMIM 606566 ), suggesting that abnormal function of skeletal MLCK stimulates cardiac hypertrophy. While phosphorylation of the putative substrate of skeletal MLCK, myosin light chain 2 (MLC2), is recognized as a key regulator of cardiac contraction, the abundance of skeletal MLCK in the heart is controversial, suggesting the existence of an additional MLCK that is preferentially expressed in cardiac muscle. Methods and Results: We characterized a new kinase named cardiac MLCK that is encoded by a gene homologous to mylk1 and 2 and is specifically expressed in the heart in both atrium and ventricle. Expression of cardiac MLCK was highly regulated by the cardiac homeobox transcription factor, Nkx2.5, in neonatal cardiomyocytes. The overall structure of cardiac MLCK protein is conserved with skeletal and smooth muscle MLCK including putative catalytic and adjacent Ca2+/calmodulin binding domains at the carboxyl-terminus. The amino-terminus is unique without significant homology to other known proteins. Cardiac MLCK phosphorylated MLC2v with a catalytic value of Km=4.3 micro M (Lineweaver-Burk analysis) indicating high affinity of cardiac MLCK to MLC2v, similar to the affinity of skeletal muscle MLCK to skeletal muscle MLC2 and smooth muscle MLCK to smooth muscle MLC2. Adenoviral-mediated overexpression of cardiac MLCK and knockdown of cardiac MLCK using RNAi in cultured cardiomyocytes revealed that cardiac MLCK regulates MLC2v phosphorylation, sarcomere organization and cardiac myocyte contraction. Expression of cardiac MLCK protein was significantly decreased in severe heart failure in vivo (post-myocardial infarction heart failure mouse model). Conclusion: Cardiac MLCK is a new key regulator of cardiac contraction and sarcomere organization. Reduction of cardiac MLCK function leading to decreased phosphorylation of MLC2v may contribute to compromised contractile function in the failing heart.

Myosin light chain kinase mediates sarcomere organization during cardiac hypertrophy in vitro

10.1038/72287 ◽  
2000 ◽  
Vol 6 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Hiroki Aoki ◽  
Junichi Sadoshima ◽  
Seigo Izumo
Keyword(s):  
Cardiac Hypertrophy ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain

scholarly journals Regulation of Myosin Light Chain Kinase Expression by Angiotensin II in Hypertension

2008 ◽  
Vol 21 (8) ◽  
pp. 860-865 ◽  
Author(s):  
Y.-J. Han ◽  
W.-Y. Hu ◽  
M. Piano ◽  
P. de Lanerolle
Keyword(s):  
Angiotensin Ii ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Expression

scholarly journals Recombinant Matrix Metalloproteinase-9 Induces Ventricular Remodeling By Up-Regulating Angiotensin II

2020 ◽  
Vol 33 (2) ◽  
pp. 205-206
Author(s):  
Lu-yuan Luo ◽  
Si-qi Gu ◽  
Wan-xing Zhou ◽  
Li-zhi Chen ◽  
Xin-chao You ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Matrix Metalloproteinase ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Serum Levels ◽  
Left Ventricular ◽  
Matrix Metalloproteinase 9 ◽  
Ang Ii ◽  
Protein Levels ◽  
Metalloproteinase 9

Abstract Objective To study the effect of matrix metalloproteinase-9 (MMP-9) on ventricular remodeling and involvement of angiotensin II (Ang II). Methods Thirty-six adult male Wistar rats were randomly divided into control (n = 12), MMP-9 (n = 12), and MMP-9 + olmesartan (n = 12) groups. Recombinant MMP-9 (2.1 ng/g) was injected intraperitoneally twice a week. Olmesartan (3 mg/kg) was given by oral gavage once daily. Animals were treated for 4 or 8 weeks. Cardiac function was assessed by echocardiography followed by histological analysis. The messenger RNA (mRNA) and protein levels of MMP-9 in myocardial tissues were analyzed by reverse transcription polymerase chain reaction and Western blotting, respectively. Serum levels of Ang I, II, angiotensin converting enzyme (ACE) and MMP-9 were determined by enzyme-linked immunosorbent assay (ELISA). Results MMP9 administration for 4 or 8 weeks increased mRNA and protein levels of MMP-9 in myocardial tissues, serum levels of MMP-9, Ang I, II and ACE, and left ventricular mass index (LVMI) but decreased collagen volume fraction (CVF) compared with the control group (all P < 0.05). Cardiomyocyte cell size was significantly enlarged and disorganized with cytoplasmic lysis and necrosis in the MMP-9 group. After olmesartan treatment, myocardial MMP-9 mRNA and protein levels, serum levels of MMP-9 and Ang II, and LVMI were lower, and CVF was higher with significant improvement in myocardial morphology and cardiac function (all P<0.05). Conclusion Recombinant MMP-9 treatment induces ventricular remodeling and cardiac dysfunction by up-regulating Ang II.

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