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Leukocytic toll-like receptor 2 knockout protects against diabetes-induced cardiac dysfunction.
Biochem Biophys Res Commun. 2018 11 30; 506(3):668-673.BB

Abstract

Diabetic cardiomyopathy is characterized by the deterioration of the myocardial function. Emerging evidences have indicated that leukocytic toll-like receptor 2 (TLR2) played an important role in the development of diabetic cardiomyopathy. Our study aimed to investigate whether TLR2 knockout (KO) exerted a cardioprotective effect in vivo. The establishment of diabetes model was set up in mice via intraperitoneal injection of streptozotocin (STZ). Results demonstrated that blocking of TLR2 significantly suppressed the enhanced left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD) and the reduced the heart rate in diabetic cardiomyopathy mice. The decreased resting cell length, PS, TPS and + dL/dt while increased TR90 and - dL/dt caused by diabetic cardiomyopathy were remarkably inhibited by TLR2 KO. Besides that, the alleviated ΔFFI (360/380), decreased SERCA2a and p-NFATc3 expressions, extended Ca2+ decay time and elevated Calcineurin A induced by diabetic cardiomyopathy were vastly repressed by TLR2 KO in cardiocytes. Moreover, TLR2 gene silence could ameliorate oxidative stress-induced apoptosis, evidences were the up-regulated superoxide generation and Bax/Bcl-2 expression while restrained GSH/GSSG ratio caused by diabetic cardiomyopathy were tremendously repressed in TLR2 KO mice. Furthermore, blocking of TLR2 remarkably attenuated the augmented fibrosis areas of heart tissues in mice with diabetic cardiomyopathy. The result of the enhanced α-SMA and collagenⅠ caused by diabetic cardiomyopathy were suppressed in heart tissues of TLR2 KO mice further validate it. All in all, our study demonstrated that diabetes-induced cardiac dysfunction could be attenuated by TLR2 KO.

Authors+Show Affiliations

Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, 637000, Sichuan Province, PR China.Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, 637000, Sichuan Province, PR China. Electronic address: huhouxiang@sohu.com.Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, 637000, Sichuan Province, PR China.Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, 637000, Sichuan Province, PR China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30454704

Citation

Lei, Lei, et al. "Leukocytic Toll-like Receptor 2 Knockout Protects Against Diabetes-induced Cardiac Dysfunction." Biochemical and Biophysical Research Communications, vol. 506, no. 3, 2018, pp. 668-673.
Lei L, Hu H, Lei Y, et al. Leukocytic toll-like receptor 2 knockout protects against diabetes-induced cardiac dysfunction. Biochem Biophys Res Commun. 2018;506(3):668-673.
Lei, L., Hu, H., Lei, Y., & Feng, J. (2018). Leukocytic toll-like receptor 2 knockout protects against diabetes-induced cardiac dysfunction. Biochemical and Biophysical Research Communications, 506(3), 668-673. https://doi.org/10.1016/j.bbrc.2018.10.082
Lei L, et al. Leukocytic Toll-like Receptor 2 Knockout Protects Against Diabetes-induced Cardiac Dysfunction. Biochem Biophys Res Commun. 2018 11 30;506(3):668-673. PubMed PMID: 30454704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Leukocytic toll-like receptor 2 knockout protects against diabetes-induced cardiac dysfunction. AU - Lei,Lei, AU - Hu,Houxiang, AU - Lei,Yan, AU - Feng,Jie, Y1 - 2018/10/26/ PY - 2018/10/08/received PY - 2018/10/13/accepted PY - 2018/11/21/entrez PY - 2018/11/21/pubmed PY - 2019/5/18/medline KW - Cardiac dysfunction KW - Cytoplasmic 3 KW - Diabetes KW - FFI KW - Fura-2 fluorescence intensity KW - GSH KW - GSSG KW - Glutathione KW - Glutathione disulfide KW - KO KW - Knockout KW - LVEDD KW - LVESD KW - Left ventricular end systolic diameter KW - Left ventricular end-diastolic dimension KW - Leukocytic toll-like receptor 2 KW - Maximal velocity of shortening/relengthening KW - NFATc3 KW - Nuclear factor of activated T-cells KW - PS KW - Peak shortening KW - SERCA2a KW - STZ KW - Sarco-endoplasmic reticulum ATPase 2a KW - Streptozotocin KW - TLR2 KW - TPS KW - TR90 KW - Time-to-90% relengthening KW - Time-to-PS KW - ±dL/dt SP - 668 EP - 673 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 506 IS - 3 N2 - Diabetic cardiomyopathy is characterized by the deterioration of the myocardial function. Emerging evidences have indicated that leukocytic toll-like receptor 2 (TLR2) played an important role in the development of diabetic cardiomyopathy. Our study aimed to investigate whether TLR2 knockout (KO) exerted a cardioprotective effect in vivo. The establishment of diabetes model was set up in mice via intraperitoneal injection of streptozotocin (STZ). Results demonstrated that blocking of TLR2 significantly suppressed the enhanced left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD) and the reduced the heart rate in diabetic cardiomyopathy mice. The decreased resting cell length, PS, TPS and + dL/dt while increased TR90 and - dL/dt caused by diabetic cardiomyopathy were remarkably inhibited by TLR2 KO. Besides that, the alleviated ΔFFI (360/380), decreased SERCA2a and p-NFATc3 expressions, extended Ca2+ decay time and elevated Calcineurin A induced by diabetic cardiomyopathy were vastly repressed by TLR2 KO in cardiocytes. Moreover, TLR2 gene silence could ameliorate oxidative stress-induced apoptosis, evidences were the up-regulated superoxide generation and Bax/Bcl-2 expression while restrained GSH/GSSG ratio caused by diabetic cardiomyopathy were tremendously repressed in TLR2 KO mice. Furthermore, blocking of TLR2 remarkably attenuated the augmented fibrosis areas of heart tissues in mice with diabetic cardiomyopathy. The result of the enhanced α-SMA and collagenⅠ caused by diabetic cardiomyopathy were suppressed in heart tissues of TLR2 KO mice further validate it. All in all, our study demonstrated that diabetes-induced cardiac dysfunction could be attenuated by TLR2 KO. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/30454704/Leukocytic_toll_like_receptor_2_knockout_protects_against_diabetes_induced_cardiac_dysfunction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(18)32238-1 DB - PRIME DP - Unbound Medicine ER -