Time-Series Change of Serum Soluble T-Cadherin Concentrations and Its Association with Creatine Kinase-MB Levels in ST-Segment Elevation Myocardial Infarction

AIMS T-cadherin (T-cad) is a specific binding partner of adiponectin (APN), adipocyte-specific secretory protein. APN exhibits organ protection via the T-cad-dependent accumulation onto several tissues such as the aorta, heart, and muscle. Recently, for the first time, we showed that three forms (130, 100, and 30 kDa) of soluble T-cad existed in human serum and correlated with several clinical parameters in patients with type 2 diabetes. Nevertheless, the significance of soluble T-cad has not been elucidated in the acute stage of cardiovascular diseases. We herein examined soluble T-cad concentrations and investigated their clinical significance in patients with emergency hospital admission due to ST-segment elevation myocardial infarction (STEMI). METHODS This observational study enrolled 47 patients with STEMI who were treated via primary percutaneous coronary intervention (PCI). Soluble T-cad and APN concentrations were measured by using an enzyme-linked immunosorbent assay. This study is registered with the University Hospital Medical Information Network (Number: UMIN 000014418). RESULTS Serum concentrations of soluble 130 and 100 kDa T-cad rapidly and significantly decreased after hospitalization and reached the bottom at 72 h after admission (p<0.001 and p<0.001, respectively). The patients with high soluble T-cad and low APN concentrations on admission showed a significantly higher area under the curve of serum creatine kinase-MB (p<0.01). CONCLUSION Serum soluble T-cad concentration changed dramatically in patients with STEMI, and the high T-cad and low APN concentrations on admission were associated with the myocardial infarction size. Further study is needed to investigate the usefulness of categorizing patients with STEMI by serum T-cad and APN for the prediction of severe prognoses.

[1]  T. Funahashi,et al.  Adiponectin, a unique adipocyte-derived factor beyond hormones. , 2019, Atherosclerosis.

[2]  Y. Matsuzawa Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease , 2006, Nature Clinical Practice Cardiovascular Medicine.

[3]  H. Lodish,et al.  T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Philippe Froguel,et al.  Cloning of adiponectin receptors that mediate antidiabetic metabolic effects , 2003, Nature.

[5]  I. Shimomura,et al.  Identification and Clinical Associations of 3 Forms of Circulating T-cadherin in Human Serum , 2021, The Journal of clinical endocrinology and metabolism.

[6]  A. Schoenenberger,et al.  Plasma T-cadherin negatively associates with coronary lesion severity and acute coronary syndrome , 2015, European heart journal. Acute cardiovascular care.

[7]  T. Lehtimäki,et al.  A longitudinal analysis on associations of adiponectin levels with metabolic syndrome and carotid artery intima-media thickness. The Cardiovascular Risk in Young Finns Study. , 2011, Atherosclerosis.

[8]  R. Puronaitė,et al.  The Role of Cardiac T-Cadherin in the Indicating Heart Failure Severity of Patients with Non-Ischemic Dilated Cardiomyopathy , 2020, Medicina.

[9]  C. Hengstenberg,et al.  Adiponectin multimeric forms but not total adiponectin levels are associated with myocardial infarction in non-diabetic men. , 2011, Journal of atherosclerosis and thrombosis.

[10]  B. Knebel,et al.  CDH13 abundance interferes with adipocyte differentiation and is a novel biomarker for adipose tissue health , 2018, International Journal of Obesity.

[11]  Y. Teo,et al.  Genetic Variation in CDH13 Is Associated With Lower Plasma Adiponectin Levels but Greater Adiponectin Sensitivity in East Asian Populations , 2013, Diabetes.

[12]  T. Funahashi,et al.  Significant Association of Serum Adiponectin and Creatine Kinase-MB Levels in ST-Segment Elevation Myocardial Infarction , 2017, Journal of atherosclerosis and thrombosis.

[13]  T. Funahashi,et al.  Adiponectin promotes muscle regeneration through binding to T-cadherin , 2019, Scientific Reports.

[14]  O. De Wever,et al.  Soluble cadherins as cancer biomarkers , 2007, Clinical & Experimental Metastasis.

[15]  I. Shimomura,et al.  Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice , 2020, Molecular Therapy.

[16]  H. Lai,et al.  Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface , 2018, Nature Communications.

[17]  Yasuhiko Tomino,et al.  Revised equations for estimated GFR from serum creatinine in Japan. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[18]  B. Ranscht,et al.  T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region , 1991, Neuron.

[19]  T. Funahashi,et al.  Positive feedback regulation between adiponectin and T-cadherin impacts adiponectin levels in tissue and plasma of male mice. , 2015, Endocrinology.

[20]  Wen-Harn Pan,et al.  A Genome-Wide Association Study Reveals a Quantitative Trait Locus of Adiponectin on CDH13 That Predicts Cardiometabolic Outcomes , 2011, Diabetes.

[21]  Cynthia J. Girman,et al.  Plasma adiponectin levels and risk of myocardial infarction in men. , 2004, JAMA.

[22]  T. Funahashi,et al.  The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism. , 2011, Journal of atherosclerosis and thrombosis.

[23]  Y. Kokubo,et al.  CDH13 gene coding t‐cadherin influences variations in plasma adiponectin levels in the Japanese population , 2012, Human mutation.

[24]  P. Wilson,et al.  Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham offspring Study. , 2011, Atherosclerosis.

[25]  R. Rizza,et al.  Selective Downregulation of the High–Molecular Weight Form of Adiponectin in Hyperinsulinemia and in Type 2 Diabetes , 2007, Diabetes.

[26]  E. Fukusaki,et al.  Adiponectin/T-cadherin system enhances exosome biogenesis and decreases cellular ceramides by exosomal release. , 2018, JCI insight.

[27]  X. Bian,et al.  Beyond a tumor suppressor: Soluble E‐cadherin promotes the progression of cancer , 2016, International journal of cancer.

[28]  M. Matsuzaki,et al.  Correlation between circulating adiponectin levels and coronary plaque regression during aggressive lipid-lowering therapy in patients with acute coronary syndrome: subgroup analysis of JAPAN-ACS study. , 2010, Atherosclerosis.

[29]  S. Kihara,et al.  Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. 1999. , 2012, Biochemical and biophysical research communications.

[30]  A. Schoenenberger,et al.  Gender-Specific Associations between Circulating T-Cadherin and High Molecular Weight-Adiponectin in Patients with Stable Coronary Artery Disease , 2015, PloS one.

[31]  T. Kitamoto,et al.  CDH13 Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome Traits Independently of Visceral Fat Mass. , 2016, Journal of atherosclerosis and thrombosis.

[32]  I. Shimomura,et al.  Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin. , 2020, American journal of physiology. Endocrinology and metabolism.

[33]  H. Hirose,et al.  Serum high-molecular-weight adiponectin as a marker for the evaluation and care of subjects with metabolic syndrome and related disorders. , 2010, Journal of atherosclerosis and thrombosis.