Progranulin deficiency leads to enhanced age-related cardiac hypertrophy through complement C1q-induced β-catenin activation

Zhu, Yinghong; Ohama, Tohru; Kawase, Ryota; Chang, Jiuyang; Inui, Haruyuki; Kanno, Kotaro; Okada, Takeshi; Masuda, Daisuke; Koseki, Masahiro; Nishida, Makoto; Sakata, Yasushi; Yamashita, Shizuya

doi:10.1016/j.yjmcc.2019.12.009

Cited by 11 publications

(16 citation statements)

References 39 publications

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“…Mice were exposed to the inhalation anesthetic isoflurane (1.5%~2%). M-mode and tissue Doppler interrogation were performed by a 30 MHz high-frequency scan head (Vevo770, VisualSonics, Toronto, Canada), and LV end-diastolic diameter (LVDd), LV end-systolic diameter (LVSd), percentage of fractional shortening (FS%), and the average ratios of E / A and E / e ′ were measured as we performed previously [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…To detect the intestinal fibrosis, sections were stained with Sirius red. For cell surface area (CSA) measurement, the sections were stained with 50 μ g/ml wheat germ agglutinin (WGA, Sigma-Aldrich, St. Louis, MO, USA) as we described previously [ 19 ]. Tissue sections were then visualized by a microscope and photographed.…”

Section: Methodsmentioning

confidence: 99%

“…The cell-type-specific markers troponin I and vimentin were costained with miR-340. For neonatal rat ventricular myocytes (NRVMs) and cardiac fibroblast preparation, a standard method was carried out as we described previously [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

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miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1

Zhu

Yang

Zhou

et al. 2022

Oxidative Medicine and Cellular Longevity

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Diabetic cardiomyopathy (DCM) is initially characterized by early diastolic dysfunction, left ventricular remodeling, hypertrophy, and myocardial fibrosis, and it is eventually characterized by clinical heart failure. MicroRNAs (miRNAs), endogenous small noncoding RNAs, play significant roles in diabetes mellitus (DM). However, it is still largely unknown about the mechanism that links miRNAs and the development of DCM. Here, we aimed to elucidate the mechanism underlying the potential role of microRNA-340-5p in DCM in db/db mouse, which is a commonly used model of type 2 DM and diabetic complications that lead to heart failure. We first demonstrated that miR-340-5p expression was dramatically increased in heart tissues of mice and cardiomyocytes under diabetic conditions. Overexpression of miR-340-5p exacerbated DCM, which was reflected by extensive myocardial fibrosis and more serious dysfunction in db/db mice as represented by increased apoptotic cardiomyocytes, elevated ROS production, and impaired mitochondrial function. Inhibition of miR-340-5p by a tough decoy (TUD) vector was beneficial for preventing ROS production and apoptosis, thus rescuing diabetic cardiomyopathy. We identified myeloid cell leukemia 1 (Mcl-1) as a major target gene for miR-340-5p and showed that the inhibition of Mcl-1 was responsible for increased functional loss of mitochondria, oxidative stress, and cardiomyocyte apoptosis, thereby caused cardiac dysfunction in diabetic mice. In conclusion, our results showed that miR-340-5p plays a crucial role in the development of DCM and can be targeted for therapeutic intervention.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1

Zhu

Yang

Zhou

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Notably, gastrointestinal issues are a common symptom in patients with PD, and mutations in GRN are implicated in cardiac dysfunction. 52,53 A systemic GT approach like HSPC-GT conceivably has advantages over other platforms including AAV GTs, where therapeutic effect is generally limited to either the periphery or the CNS. However, if CNS-restricted expression is therapeutically advantageous, our data suggest that i.c.v.…”

Section: Discussionmentioning

confidence: 99%

High-throughput analysis of hematopoietic stem cell engraftment after intravenous and intracerebroventricular dosing

et al. 2022

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“…Kojima et al first detected the expression of PGRN in atherosclerotic plaques [9]. In animal models, PGRN deficiency leads to severe atherosclerotic lesions and increased age-related myocardial hypertrophy [10,11].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of Circulating Progranulin and Its Receptor EphA2 in Predicting the Atheroma Burden in Patients with Coronary Artery Disease

et al. 2021

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Background. Progranulin (PGRN) and its potential receptor Eph-receptor tyrosine kinase-type A2 (EphA2) are inflammation-related molecules that present on the atherosclerotic plaques. However, the roles of circulating PGRN and EphA2 in coronary artery disease (CAD) remain unclear. Objective. To study the clinical significance of circulating PGRN and EphA2 levels in Chinese patients undergoing coronary angiography. Methods. Levels of circulating EphA2 fragments and PGRN were examined in 201 consecutive individuals who underwent coronary angiography for suspected CAD in our center from Jan 2020 to Oct 2020. Demographic characteristics, results of biochemical and auxiliary examinations, and other relevant information were collected. The coronary atheroma burden was quantified by the Gensini score and the existence of chronic total occlusion (CTO). Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors for acute coronary syndrome (ACS). In patients with ACS and SAP, a receiver operating characteristic (ROC) curve was generated to detect the accuracy and discriminative ability of levels of EphA2 and PGRN, the Gensini score, and cardiac injury biomarkers as surrogate endpoints for CTO. Results. Circulating EphA2 levels were significantly higher in patients with ACS than in subjects with stable angina pectoris (SAP) or control subjects ( p < 0.001 ). A positive linear correlation was verified between EphA2 levels and the Gensini score ( r = 0.306 , p < 0.001 ), and negative correlation was detected with the left ventricular ejection fraction (LVEF) ( r = − 0.405 , p < 0.001 ). Both PGRN and EphA2 were positively associated with cardiac injury biomarkers (i.e., NT-proBNP, cTnT, and hs-CRP) ( p < 0.05 ). The area under the ROC curve of PGRN and EphA2 was 0.604 and 0.686, respectively ( p < 0.01 ). Conclusions. Higher circulating EphA2 and PGRN levels were detected in patients with ACS than in patients with SAP. Circulating EphA2 and PGRN levels might be diagnostic factors for predicting the atheroma burden in patients with CAD.

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Progranulin deficiency leads to enhanced age-related cardiac hypertrophy through complement C1q-induced β-catenin activation

Cited by 11 publications

References 39 publications

miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1

miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1

High-throughput analysis of hematopoietic stem cell engraftment after intravenous and intracerebroventricular dosing

Diagnostic Value of Circulating Progranulin and Its Receptor EphA2 in Predicting the Atheroma Burden in Patients with Coronary Artery Disease

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