G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy
Background G protein‐coupled receptor kinase‐2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic car...
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| Veröffentlicht in: | Journal of diabetes 2020-03, Vol.12 (3), p.247-258 |
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| creator | Lai, Shuiqing Fu, Xiaoying Yang, Shufen Zhang, Shuting Lin, Qiuxiong Zhang, Mengzhen Chen, Hongmei |
| description | Background
G protein‐coupled receptor kinase‐2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).
Methods
C57BL/KS‐db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated. Forty‐four T2DM patients with left ventricular diastolic dysfunction (LVDD), without evidence of hypertension, coronary artery diseases, congestive heart failure, and diabetic complications and without evidence of ischemia in a maximal treadmill exercise test, were recruited as the DM + LVDD group; 30 age‐matched T2DM patients without LVDD were recruited as the DM control group. Left ventricular diastolic function was evaluated by cardiac tissue Doppler. The pseudonormal pattern of ventricular filling and E′/A′ |
| doi_str_mv | 10.1111/1753-0407.12991 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7064927</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2357028346</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4671-f9e9bc4463d4fd7d3cfb3ae0b68600914e2c62e0494bc3d553b5648a0bf6b11c3</originalsourceid><addsrcrecordid>eNqFkc1O3DAUha0KVGDKmh2yxKabAf_FGbNAolAoFVI37drYzg0YMnGwk1bZ8Qg8Y58ETwdGhQ3e2Lrn89E9OgjtULJP8zmgZcGnRJBynzKl6Ae0uZqsvby54htoK6VbQmQpJf-INjiVMyIKsomuznEXQw--_fvw6MLQNVDhCA66PkR851uTICvsEB_jLnNt702DrQ9zE-8g4jpTYGIz4sobC7132JlYZX0Mnelvxk9ovTZNgu3ne4J-nX39efJtevnj_OLk-HLqhCzptFagrBNC8krUVVlxV1tugFg5k4QoKoA5yYAIJazjVVFwW0gxM8TW0lLq-AQdLX27wc6hcnnTaBrdRZ83HXUwXr9WWn-jr8NvXRIpFCuzwedngxjuB0i9nvvkoGlMC2FImnFKFWOEs4zuvUFvwxDbHC9TRUnYjOcgE3SwpFwMKUWoV8tQohft6UU_etGV_tde_rH7f4YV_1JXBool8Mc3ML7np7-fflkaPwFwEqc4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2357028346</pqid></control><display><type>article</type><title>G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Lai, Shuiqing ; Fu, Xiaoying ; Yang, Shufen ; Zhang, Shuting ; Lin, Qiuxiong ; Zhang, Mengzhen ; Chen, Hongmei</creator><creatorcontrib>Lai, Shuiqing ; Fu, Xiaoying ; Yang, Shufen ; Zhang, Shuting ; Lin, Qiuxiong ; Zhang, Mengzhen ; Chen, Hongmei</creatorcontrib><description>Background
G protein‐coupled receptor kinase‐2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).
Methods
C57BL/KS‐db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated. Forty‐four T2DM patients with left ventricular diastolic dysfunction (LVDD), without evidence of hypertension, coronary artery diseases, congestive heart failure, and diabetic complications and without evidence of ischemia in a maximal treadmill exercise test, were recruited as the DM + LVDD group; 30 age‐matched T2DM patients without LVDD were recruited as the DM control group. Left ventricular diastolic function was evaluated by cardiac tissue Doppler. The pseudonormal pattern of ventricular filling and E′/A′ < 1 were regarded as LVDD.
Results
Compared to 8‐week‐old diabetic mice and 12‐week‐old control mice, GRK2‐mRNA level and expression in myocardial tissues of 12‐week‐old diabetic mice were significantly increased, as well as the left ventricular wall thickness and systolic function. And the collagen volume fraction (CVF), collagen‐3 expression, P53 expression, and cell apoptotic rate in the myocardium of 12‐week‐old diabetic mice elevated as well. The GRK2‐mRNA level in PBMCs of DM with LVDD was significantly higher than in DM control without LVDD.
Conclusions
GRK2 expression increased in the myocardial tissue and the PBMCs at the early stage of DCM. These data support further research on the role of GRK2 as the clinical biomarker for early DCM.
摘要
背景
研究显示G蛋白偶联受体激酶2(GRK2)是调节心脏功能的关键因子, 而心肌GRK2的表达水平与外周血单核细胞(PBMC)的GRK2表达存在一致性。本研究评估了早期糖尿病性心肌病(DCM)PBMC的GRK2水平。
方法
动物研究以12周龄的C57BL/KS‐db/db雄性糖尿病小鼠作为早期DCM的2型糖尿病(T2DM)研究模型。人群研究中招募了44位T2DM伴有左心室舒张功能障碍(LVDD)的患者为DM + LVDD组, 他们均排除了高血压、冠状动脉疾病、充血性心力衰竭和糖尿病并发症等疾病, 并且在心脏运动负荷测试中没有缺血迹象。另外招募 30位年龄相匹配的无LVDD的T2DM患者为DM对照组。左心室舒张功能通过心脏组织多普勒评估。心室假性正常化充盈和E’/A’ <1定义为LVDD。
结果
本研究结果显示, 与8周龄糖尿病小鼠和12周龄对照小鼠相比, 12周龄糖尿病小鼠心肌组织中GRK2‐mRNA水平及其表达明显增加, 且左心室壁厚度增加和收缩功能增强。胶原蛋白的体积分数(CVF)、胶原蛋白3、P53表达水平和细胞凋亡率在12周龄糖尿病小鼠心肌中也明显升高。人群研究显示, 与DM对照组患者相比, DM+LVDD组患者PBMC中GRK2‐mRNA水平明显升高。
结论
在DCM的早期阶段, 心肌组织和PBMC的GRK2水平增加。这些数据支持进一步探讨GRK2在早期DCM诊断中作为临床标志物的可能性。
Highlights
The GRK2 level elevated not only in the myocardium of diabetic mice with early stage of diabetic cardiomyopathy but also in the peripheral blood mononuclear cells of type 2 diabetic patients with the early stage of diabetic cardiomyopathy.
The study findings suggested that the GRK2 was a potential biomarker for early diabetic cardiomyopathy.</description><identifier>ISSN: 1753-0393</identifier><identifier>EISSN: 1753-0407</identifier><identifier>DOI: 10.1111/1753-0407.12991</identifier><identifier>PMID: 31680450</identifier><language>eng</language><publisher>Melbourne: Wiley Publishing Asia Pty Ltd</publisher><subject>Adult ; Animals ; Apoptosis - genetics ; Biomarkers ; Biomarkers - metabolism ; Cardiomyopathy ; Cells, Cultured ; Diabetes ; Diabetes Mellitus, Type 2 - complications ; Diabetic Cardiomyopathies - diagnosis ; Diabetic Cardiomyopathies - etiology ; Diabetic Cardiomyopathies - metabolism ; diabetic cardiomyopathy ; Diastole ; Female ; G-Protein-Coupled Receptor Kinase 2 - genetics ; G-Protein-Coupled Receptor Kinase 2 - metabolism ; Gene Expression ; GRK2 ; G蛋白偶联受体激酶2 ; Humans ; Kinases ; left ventricular diastolic dysfunction ; Male ; Mice, Inbred C57BL ; Middle Aged ; myocardium ; Myocardium - metabolism ; Myocardium - pathology ; Original ; peripheral blood mononuclear cells ; Ventricular Dysfunction, Left - diagnosis ; Ventricular Dysfunction, Left - etiology ; Ventricular Dysfunction, Left - metabolism ; 外周血单核细胞 ; 左心室舒张功能不全 ; 心肌组织 ; 糖尿病心肌病</subject><ispartof>Journal of diabetes, 2020-03, Vol.12 (3), p.247-258</ispartof><rights>2019 The Authors. published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.</rights><rights>2019 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.</rights><rights>2020 John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4671-f9e9bc4463d4fd7d3cfb3ae0b68600914e2c62e0494bc3d553b5648a0bf6b11c3</citedby><cites>FETCH-LOGICAL-c4671-f9e9bc4463d4fd7d3cfb3ae0b68600914e2c62e0494bc3d553b5648a0bf6b11c3</cites><orcidid>0000-0002-2157-4420</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1411,11541,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31680450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Shuiqing</creatorcontrib><creatorcontrib>Fu, Xiaoying</creatorcontrib><creatorcontrib>Yang, Shufen</creatorcontrib><creatorcontrib>Zhang, Shuting</creatorcontrib><creatorcontrib>Lin, Qiuxiong</creatorcontrib><creatorcontrib>Zhang, Mengzhen</creatorcontrib><creatorcontrib>Chen, Hongmei</creatorcontrib><title>G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy</title><title>Journal of diabetes</title><addtitle>J Diabetes</addtitle><description>Background
G protein‐coupled receptor kinase‐2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).
Methods
C57BL/KS‐db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated. Forty‐four T2DM patients with left ventricular diastolic dysfunction (LVDD), without evidence of hypertension, coronary artery diseases, congestive heart failure, and diabetic complications and without evidence of ischemia in a maximal treadmill exercise test, were recruited as the DM + LVDD group; 30 age‐matched T2DM patients without LVDD were recruited as the DM control group. Left ventricular diastolic function was evaluated by cardiac tissue Doppler. The pseudonormal pattern of ventricular filling and E′/A′ < 1 were regarded as LVDD.
Results
Compared to 8‐week‐old diabetic mice and 12‐week‐old control mice, GRK2‐mRNA level and expression in myocardial tissues of 12‐week‐old diabetic mice were significantly increased, as well as the left ventricular wall thickness and systolic function. And the collagen volume fraction (CVF), collagen‐3 expression, P53 expression, and cell apoptotic rate in the myocardium of 12‐week‐old diabetic mice elevated as well. The GRK2‐mRNA level in PBMCs of DM with LVDD was significantly higher than in DM control without LVDD.
Conclusions
GRK2 expression increased in the myocardial tissue and the PBMCs at the early stage of DCM. These data support further research on the role of GRK2 as the clinical biomarker for early DCM.
摘要
背景
研究显示G蛋白偶联受体激酶2(GRK2)是调节心脏功能的关键因子, 而心肌GRK2的表达水平与外周血单核细胞(PBMC)的GRK2表达存在一致性。本研究评估了早期糖尿病性心肌病(DCM)PBMC的GRK2水平。
方法
动物研究以12周龄的C57BL/KS‐db/db雄性糖尿病小鼠作为早期DCM的2型糖尿病(T2DM)研究模型。人群研究中招募了44位T2DM伴有左心室舒张功能障碍(LVDD)的患者为DM + LVDD组, 他们均排除了高血压、冠状动脉疾病、充血性心力衰竭和糖尿病并发症等疾病, 并且在心脏运动负荷测试中没有缺血迹象。另外招募 30位年龄相匹配的无LVDD的T2DM患者为DM对照组。左心室舒张功能通过心脏组织多普勒评估。心室假性正常化充盈和E’/A’ <1定义为LVDD。
结果
本研究结果显示, 与8周龄糖尿病小鼠和12周龄对照小鼠相比, 12周龄糖尿病小鼠心肌组织中GRK2‐mRNA水平及其表达明显增加, 且左心室壁厚度增加和收缩功能增强。胶原蛋白的体积分数(CVF)、胶原蛋白3、P53表达水平和细胞凋亡率在12周龄糖尿病小鼠心肌中也明显升高。人群研究显示, 与DM对照组患者相比, DM+LVDD组患者PBMC中GRK2‐mRNA水平明显升高。
结论
在DCM的早期阶段, 心肌组织和PBMC的GRK2水平增加。这些数据支持进一步探讨GRK2在早期DCM诊断中作为临床标志物的可能性。
Highlights
The GRK2 level elevated not only in the myocardium of diabetic mice with early stage of diabetic cardiomyopathy but also in the peripheral blood mononuclear cells of type 2 diabetic patients with the early stage of diabetic cardiomyopathy.
The study findings suggested that the GRK2 was a potential biomarker for early diabetic cardiomyopathy.</description><subject>Adult</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Cardiomyopathy</subject><subject>Cells, Cultured</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetic Cardiomyopathies - diagnosis</subject><subject>Diabetic Cardiomyopathies - etiology</subject><subject>Diabetic Cardiomyopathies - metabolism</subject><subject>diabetic cardiomyopathy</subject><subject>Diastole</subject><subject>Female</subject><subject>G-Protein-Coupled Receptor Kinase 2 - genetics</subject><subject>G-Protein-Coupled Receptor Kinase 2 - metabolism</subject><subject>Gene Expression</subject><subject>GRK2</subject><subject>G蛋白偶联受体激酶2</subject><subject>Humans</subject><subject>Kinases</subject><subject>left ventricular diastolic dysfunction</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>myocardium</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Original</subject><subject>peripheral blood mononuclear cells</subject><subject>Ventricular Dysfunction, Left - diagnosis</subject><subject>Ventricular Dysfunction, Left - etiology</subject><subject>Ventricular Dysfunction, Left - metabolism</subject><subject>外周血单核细胞</subject><subject>左心室舒张功能不全</subject><subject>心肌组织</subject><subject>糖尿病心肌病</subject><issn>1753-0393</issn><issn>1753-0407</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1O3DAUha0KVGDKmh2yxKabAf_FGbNAolAoFVI37drYzg0YMnGwk1bZ8Qg8Y58ETwdGhQ3e2Lrn89E9OgjtULJP8zmgZcGnRJBynzKl6Ae0uZqsvby54htoK6VbQmQpJf-INjiVMyIKsomuznEXQw--_fvw6MLQNVDhCA66PkR851uTICvsEB_jLnNt702DrQ9zE-8g4jpTYGIz4sobC7132JlYZX0Mnelvxk9ovTZNgu3ne4J-nX39efJtevnj_OLk-HLqhCzptFagrBNC8krUVVlxV1tugFg5k4QoKoA5yYAIJazjVVFwW0gxM8TW0lLq-AQdLX27wc6hcnnTaBrdRZ83HXUwXr9WWn-jr8NvXRIpFCuzwedngxjuB0i9nvvkoGlMC2FImnFKFWOEs4zuvUFvwxDbHC9TRUnYjOcgE3SwpFwMKUWoV8tQohft6UU_etGV_tde_rH7f4YV_1JXBool8Mc3ML7np7-fflkaPwFwEqc4</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Lai, Shuiqing</creator><creator>Fu, Xiaoying</creator><creator>Yang, Shufen</creator><creator>Zhang, Shuting</creator><creator>Lin, Qiuxiong</creator><creator>Zhang, Mengzhen</creator><creator>Chen, Hongmei</creator><general>Wiley Publishing Asia Pty Ltd</general><general>John Wiley & Sons, Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2157-4420</orcidid></search><sort><creationdate>202003</creationdate><title>G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy</title><author>Lai, Shuiqing ; Fu, Xiaoying ; Yang, Shufen ; Zhang, Shuting ; Lin, Qiuxiong ; Zhang, Mengzhen ; Chen, Hongmei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4671-f9e9bc4463d4fd7d3cfb3ae0b68600914e2c62e0494bc3d553b5648a0bf6b11c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>Biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Cardiomyopathy</topic><topic>Cells, Cultured</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetic Cardiomyopathies - diagnosis</topic><topic>Diabetic Cardiomyopathies - etiology</topic><topic>Diabetic Cardiomyopathies - metabolism</topic><topic>diabetic cardiomyopathy</topic><topic>Diastole</topic><topic>Female</topic><topic>G-Protein-Coupled Receptor Kinase 2 - genetics</topic><topic>G-Protein-Coupled Receptor Kinase 2 - metabolism</topic><topic>Gene Expression</topic><topic>GRK2</topic><topic>G蛋白偶联受体激酶2</topic><topic>Humans</topic><topic>Kinases</topic><topic>left ventricular diastolic dysfunction</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>myocardium</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Original</topic><topic>peripheral blood mononuclear cells</topic><topic>Ventricular Dysfunction, Left - diagnosis</topic><topic>Ventricular Dysfunction, Left - etiology</topic><topic>Ventricular Dysfunction, Left - metabolism</topic><topic>外周血单核细胞</topic><topic>左心室舒张功能不全</topic><topic>心肌组织</topic><topic>糖尿病心肌病</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lai, Shuiqing</creatorcontrib><creatorcontrib>Fu, Xiaoying</creatorcontrib><creatorcontrib>Yang, Shufen</creatorcontrib><creatorcontrib>Zhang, Shuting</creatorcontrib><creatorcontrib>Lin, Qiuxiong</creatorcontrib><creatorcontrib>Zhang, Mengzhen</creatorcontrib><creatorcontrib>Chen, Hongmei</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of diabetes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Shuiqing</au><au>Fu, Xiaoying</au><au>Yang, Shufen</au><au>Zhang, Shuting</au><au>Lin, Qiuxiong</au><au>Zhang, Mengzhen</au><au>Chen, Hongmei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy</atitle><jtitle>Journal of diabetes</jtitle><addtitle>J Diabetes</addtitle><date>2020-03</date><risdate>2020</risdate><volume>12</volume><issue>3</issue><spage>247</spage><epage>258</epage><pages>247-258</pages><issn>1753-0393</issn><eissn>1753-0407</eissn><abstract>Background
G protein‐coupled receptor kinase‐2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).
Methods
C57BL/KS‐db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated. Forty‐four T2DM patients with left ventricular diastolic dysfunction (LVDD), without evidence of hypertension, coronary artery diseases, congestive heart failure, and diabetic complications and without evidence of ischemia in a maximal treadmill exercise test, were recruited as the DM + LVDD group; 30 age‐matched T2DM patients without LVDD were recruited as the DM control group. Left ventricular diastolic function was evaluated by cardiac tissue Doppler. The pseudonormal pattern of ventricular filling and E′/A′ < 1 were regarded as LVDD.
Results
Compared to 8‐week‐old diabetic mice and 12‐week‐old control mice, GRK2‐mRNA level and expression in myocardial tissues of 12‐week‐old diabetic mice were significantly increased, as well as the left ventricular wall thickness and systolic function. And the collagen volume fraction (CVF), collagen‐3 expression, P53 expression, and cell apoptotic rate in the myocardium of 12‐week‐old diabetic mice elevated as well. The GRK2‐mRNA level in PBMCs of DM with LVDD was significantly higher than in DM control without LVDD.
Conclusions
GRK2 expression increased in the myocardial tissue and the PBMCs at the early stage of DCM. These data support further research on the role of GRK2 as the clinical biomarker for early DCM.
摘要
背景
研究显示G蛋白偶联受体激酶2(GRK2)是调节心脏功能的关键因子, 而心肌GRK2的表达水平与外周血单核细胞(PBMC)的GRK2表达存在一致性。本研究评估了早期糖尿病性心肌病(DCM)PBMC的GRK2水平。
方法
动物研究以12周龄的C57BL/KS‐db/db雄性糖尿病小鼠作为早期DCM的2型糖尿病(T2DM)研究模型。人群研究中招募了44位T2DM伴有左心室舒张功能障碍(LVDD)的患者为DM + LVDD组, 他们均排除了高血压、冠状动脉疾病、充血性心力衰竭和糖尿病并发症等疾病, 并且在心脏运动负荷测试中没有缺血迹象。另外招募 30位年龄相匹配的无LVDD的T2DM患者为DM对照组。左心室舒张功能通过心脏组织多普勒评估。心室假性正常化充盈和E’/A’ <1定义为LVDD。
结果
本研究结果显示, 与8周龄糖尿病小鼠和12周龄对照小鼠相比, 12周龄糖尿病小鼠心肌组织中GRK2‐mRNA水平及其表达明显增加, 且左心室壁厚度增加和收缩功能增强。胶原蛋白的体积分数(CVF)、胶原蛋白3、P53表达水平和细胞凋亡率在12周龄糖尿病小鼠心肌中也明显升高。人群研究显示, 与DM对照组患者相比, DM+LVDD组患者PBMC中GRK2‐mRNA水平明显升高。
结论
在DCM的早期阶段, 心肌组织和PBMC的GRK2水平增加。这些数据支持进一步探讨GRK2在早期DCM诊断中作为临床标志物的可能性。
Highlights
The GRK2 level elevated not only in the myocardium of diabetic mice with early stage of diabetic cardiomyopathy but also in the peripheral blood mononuclear cells of type 2 diabetic patients with the early stage of diabetic cardiomyopathy.
The study findings suggested that the GRK2 was a potential biomarker for early diabetic cardiomyopathy.</abstract><cop>Melbourne</cop><pub>Wiley Publishing Asia Pty Ltd</pub><pmid>31680450</pmid><doi>10.1111/1753-0407.12991</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2157-4420</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1753-0393 |
| ispartof | Journal of diabetes, 2020-03, Vol.12 (3), p.247-258 |
| issn | 1753-0393 1753-0407 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7064927 |
| source | MEDLINE; Wiley Online Library Open Access; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Animals Apoptosis - genetics Biomarkers Biomarkers - metabolism Cardiomyopathy Cells, Cultured Diabetes Diabetes Mellitus, Type 2 - complications Diabetic Cardiomyopathies - diagnosis Diabetic Cardiomyopathies - etiology Diabetic Cardiomyopathies - metabolism diabetic cardiomyopathy Diastole Female G-Protein-Coupled Receptor Kinase 2 - genetics G-Protein-Coupled Receptor Kinase 2 - metabolism Gene Expression GRK2 G蛋白偶联受体激酶2 Humans Kinases left ventricular diastolic dysfunction Male Mice, Inbred C57BL Middle Aged myocardium Myocardium - metabolism Myocardium - pathology Original peripheral blood mononuclear cells Ventricular Dysfunction, Left - diagnosis Ventricular Dysfunction, Left - etiology Ventricular Dysfunction, Left - metabolism 外周血单核细胞 左心室舒张功能不全 心肌组织 糖尿病心肌病 |
| title | G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T16%3A28%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=G%20protein%E2%80%90coupled%20receptor%20kinase%E2%80%902:%20A%20potential%20biomarker%20for%20early%20diabetic%20cardiomyopathy&rft.jtitle=Journal%20of%20diabetes&rft.au=Lai,%20Shuiqing&rft.date=2020-03&rft.volume=12&rft.issue=3&rft.spage=247&rft.epage=258&rft.pages=247-258&rft.issn=1753-0393&rft.eissn=1753-0407&rft_id=info:doi/10.1111/1753-0407.12991&rft_dat=%3Cproquest_pubme%3E2357028346%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2357028346&rft_id=info:pmid/31680450&rfr_iscdi=true |