Plasma Connective Tissue Growth Factor (CTGF/CCN2) Levels Predict Myocardial Infarction in the Veterans Affairs Diabetes Trial (VADT) Cohort

Hunt, Kelly J.; Jaffa, Miran A.; Garrett, Steven L.; Luttrell, Deirdre K.; Lipson, Kenneth E.; Lopes‐Virella, Maria F.; Luttrell, Louis M.; Jaffa, Ayad A.; Baker, Nathaniel L.; Virella, Gabriel; Möritz, Thomas

doi:10.2337/dc17-2083

Cited by 20 publications

(13 citation statements)

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“…CCN family member 2 (CCN2) (also known as connective tissue growth factor [CTGF]) acts as a multifunctional signaling modulator in various biologic or pathologic processes (Luft, ). Aberrant CCN2 expression has been found in lung fibrosis (X. Li et al, ), oral submucosal fibrosis (Gottipamula, Sundarrajan, Moorthy, Padmanabhan, & N Sridhar, ), pulmonary hypertension (Pi et al, ), autosomal‐dominant polycystic kidney disease (Gauer et al, ), and in inflammatory and fibroproliferative disorders (Hunt et al, ). CCN2 is also thought to be involved in tumor cell angiogenesis, proliferation, migration, metastasis, and chemoresistance (Brigstock, ; Leask & Abraham, ; Zeng et al, ).…”

Section: Introductionmentioning

confidence: 99%

CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression

Tsai

Chang

Tsai

et al. 2018

Journal Cellular Physiology

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In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP‐binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6β1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR‐519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6β1 integrin receptor, whereas CCN2 downregulates miR‐519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression

Tsai

Chang

Tsai

et al. 2018

Journal Cellular Physiology

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“…Studies have shown that the expression of CTGF was increased in cardiac tissue of patients with cardiomyopathy or heart failure [9,16]. In addition, a study recently demonstrated that the plasma levels of CTGF were higher in patients with diabetes who were susceptible to MI and cardiovascular events [19]. All of the above mentioned aspects indicate that CTGF plays an important role in the pathogenesis of cardiac disease, Whereas, the relationship between the plasma CTGF levels and risk of HHD in human remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a recent study showed that high levels of CTGF can predict the risk of future myocardial infarction (MI) and cardiovascular death in patients with type 2 diabetes [19]. However, the circulating CTGF levels have not been investigated in hyperthyroidism patients with or without HHD .…”

Section: Introductionmentioning

confidence: 99%

The association of plasma connective tissue growth factor (CTGF) levels with hyperthyroidism heart disease: a cross-sectional observational study

Zeng

Liao

et al. 2020

Preprint

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Background: Hyperthyroidism heart disease (HHD) is the most severe complication of overt hyperthyroidism and increases the mortality risk in affected patients. Early identification of patients at a higher risk of developing HHD could improve clinical outcomes through active surveillance and management. Connective tissue growth factor (CTGF), a secreted extracellular protein, plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the relationship between plasma CTGF level and the risk of HHD in this study.Methods: A total of 142 overt hyperthyroidism patients without HHD and 99 patients with HHD were included. The plasma CTGF levels were measured via ELISA. Routine clinical medical data and echocardiography parameters were also recorded.Results: The plasma CTGF level was significantly higher in patients with HHD than in those without HHD (P = 0.002) and positively correlated with the levels of FT3, TRAb, TnI, LDH and the left atrium diameter, right atrium diameter, and right ventricular end-diastolic diameter(all P < 0.05). Logistic regression analysis showed that quartile 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD (crude OR 2.529; 95% CI 1.188-5.387). However, after adjustment for the potentially confounding variables, only quartile 4 was significantly associated with the higher risk of HHD relative to quartile 1.Conclusions: Hyperthyroidism patients with HHD display higher plasma CTGF levels. Furthermore, CTGF is an independent risk factor for HHD. Therefore, the plasma CTGF level may be a potential biomarker for the risk of HHD.

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“…[29][30][31][32] Thus, the risk factors of cancer have been transferred from pollution or infection to consumption of tobacco and alcohol, excessive nutrition and physical inactivity; the latter also promotes death related to diabetes-and cardio-cerebrovascular disease, possibly by inducing systemic inflammation. 33,34 The proportion of deaths related to cardio-cerebrovascular disease or cancer has continued to increase over the past 42 years. This trend is projected to continue in the future.…”

Section: Discussionmentioning

confidence: 99%

Influence of socioeconomic events on cause-specific mortality in urban Shanghai, China, from 1974 to 2015: a population-based longitudinal study

Wang

Han

et al. 2018

CMAJ

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Plasma Connective Tissue Growth Factor (CTGF/CCN2) Levels Predict Myocardial Infarction in the Veterans Affairs Diabetes Trial (VADT) Cohort

Abstract: Our study indicates that high levels of CTGF/CCN2 predict future MI and cardiovascular death in patients with type 2 diabetes.

Cited by 20 publications

References 40 publications

CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression

CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression

The association of plasma connective tissue growth factor (CTGF) levels with hyperthyroidism heart disease: a cross-sectional observational study

Influence of socioeconomic events on cause-specific mortality in urban Shanghai, China, from 1974 to 2015: a population-based longitudinal study

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