HMGCS2 is a key ketogenic enzyme potentially involved in type 1 diabetes with high cardiovascular risk

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentia...

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Published in:	Scientific reports Vol. 7; no. 1; pp. 4590 - 10
Main Authors:	Shukla, Sanket Kumar, Liu, Weijing, Sikder, Kunal, Addya, Sankar, Sarkar, Amrita, Wei, Yidong, Rafiq, Khadija
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 04.07.2017 Nature Publishing Group Nature Portfolio
Subjects:	38 38/61 38/77 59 631/114 631/1647 631/337 64 64/60 692/4019 692/53 82 82/80 96 Animals Apoptosis Cardiovascular diseases Cardiovascular Diseases - diagnosis Cardiovascular Diseases - genetics Cardiovascular Diseases - metabolism Cardiovascular Diseases - physiopathology Computational Biology - methods Diabetes Diabetes mellitus Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 1 - metabolism DNA microarrays Echocardiography Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks Health risks Heart Heart diseases Hemodynamics Humanities and Social Sciences Humans Hydroxymethylglutaryl-CoA Synthase - genetics Hydroxymethylglutaryl-CoA Synthase - metabolism Hyperglycemia Ketogenesis Ketone Bodies - biosynthesis Kidneys Male Mice Molecular Sequence Annotation Mortality risk multidisciplinary Ribonucleic acid RNA Science Science (multidisciplinary) Spleen Toxicology Transcriptome Vascular diseases
ISSN:	2045-2322, 2045-2322
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Abstract	Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 ( HMGCS2 ) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction.
AbstractList	Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction. Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction.Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction. Abstract Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction. Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 ( HMGCS2 ) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction.
ArticleNumber	4590
Author	Addya, Sankar Liu, Weijing Sarkar, Amrita Sikder, Kunal Wei, Yidong Rafiq, Khadija Shukla, Sanket Kumar
Author_xml	– sequence: 1 givenname: Sanket Kumar surname: Shukla fullname: Shukla, Sanket Kumar organization: Department of Medicine, Center of Translational Medicine, Thomas Jefferson University – sequence: 2 givenname: Weijing surname: Liu fullname: Liu, Weijing organization: Internal Medicine-Cardiovascular Department, Shanghai Tenth People’s Hospital – sequence: 3 givenname: Kunal surname: Sikder fullname: Sikder, Kunal organization: Department of Medicine, Center of Translational Medicine, Thomas Jefferson University – sequence: 4 givenname: Sankar surname: Addya fullname: Addya, Sankar organization: Kimmel Cancer Centre, Thomas Jefferson University – sequence: 5 givenname: Amrita surname: Sarkar fullname: Sarkar, Amrita organization: Department of Medicine, Center of Translational Medicine, Thomas Jefferson University – sequence: 6 givenname: Yidong surname: Wei fullname: Wei, Yidong organization: Department of Cardiology, Shanghai Tenth People’s Hospital of Tongji University – sequence: 7 givenname: Khadija surname: Rafiq fullname: Rafiq, Khadija email: Khadija.Rafiq@jefferson.edu organization: Department of Medicine, Center of Translational Medicine, Thomas Jefferson University
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ZhangDProteomics analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetesAJP: Endocrinology and Metabolism20113002E287E2952011AIPC.1376..287Z1:CAS:528:DC%2BC3MXisFyjurk%3D Eckel-MahanKSassone-CorsiPMetabolism and the Circadian Clock ConvergePhysiological Reviews20139311071351:CAS:528:DC%2BC3sXhvFKns74%3D10.1152/physrev.00016.2012233039073781773 HuntKJLongitudinal Association Between Endothelial Dysfunction, Inflammation, and Clotting Biomarkers With Subclinical Atherosclerosis in Type 1 Diabetes: An Evaluation of the DCCT/EDIC CohortDiabetes Care2015387128112891:CAS:528:DC%2BC2MXhs1Wiur3J10.2337/dc14-2877258522104477339 KaurPReisMDCouchmanGRForjuohSNGreeneJFSERPINE 1 Links Obesity and Diabetes: A Pilot StudyJournal of Proteomics & Bioinformatics201003061911991:CAS:528:DC%2BC3cXos1aru7g%3D10.4172/jpb.1000139 Marie Paschaki et al. Transcriptomic Analysis of Murine Embryos Lacking Endogenous Retinoic Acid Signaling. PLoS ONE8(4), e62274 (2013). D. G. Cotter, R. C. 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Snippet	Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk... Abstract Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the...
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Title	HMGCS2 is a key ketogenic enzyme potentially involved in type 1 diabetes with high cardiovascular risk
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