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  1. Article ; Online: Prescribing cascades of antigout medications from thiazide diuretics in gout-naïve hypertensive adults receiving first-line pharmacological management.

    Lu, Shang-Yeh / Hsu, Hsing-Yu / Hsieh, Yow-Wen / Lu, Chiung-Ray / Huang, Hsin-Yi / Chang, Shih-Sheng

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 7402

    Abstract: Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the ... ...

    Abstract Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the pharmacological treatment. This population-based, retrospective cohort study used the Taiwan National Health Insurance Registry Database. Gout-naïve hypertensive adults who were newly dispensed first-line antihypertensive drugs between January 1, 2000, and December 31, 2016, were enrolled. Patients were divided into the thiazide group (n = 4192) and the non-thiazide group (n = 81,083). The non-thiazide group included patients who received an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-blocker. The study utilized propensity score matching and multivariable Cox regression models to investigate the prescribing cascade of antigout agents following antihypertensive treatment, adjusting for factors like age, sex, comorbidities, and concurrent medications. After propensity score matching, each group consisted of 4045 patients, with the thiazide group exhibiting a higher risk of being prescribed antigout medications across different time intervals post-treatment initiation. Specifically, adjusted hazard ratios (aHRs) for the thiazide group were 2.23, 2.07, and 2.41 for < 30 days, 31-180 days, and > 180 days, respectively, indicating a sustained and significant risk over time. Comparative analyses revealed thiazide diuretics were associated with a higher risk of antigout medication prescriptions compared to other antihypertensive classes, particularly evident after 180 days. Subgroup analyses across various demographics and comorbidities consistently showed an increased risk in the thiazide cohort. Gout-naïve hypertensive adults newly dispensed thiazide had a higher risk of subsequently adding antigout agents than those taking other first-line antihypertensive medications. The awareness and interruption of these prescribing cascades are critical to improving patient safety.
    MeSH term(s) Adult ; Humans ; Antihypertensive Agents/therapeutic use ; Sodium Chloride Symporter Inhibitors/therapeutic use ; Retrospective Studies ; Hypertension/drug therapy ; Hypertension/epidemiology ; Hypertension/chemically induced ; Calcium Channel Blockers/therapeutic use ; Thiazides/therapeutic use ; Gout/drug therapy ; Gout/complications ; Gout Suppressants/therapeutic use ; Diuretics/therapeutic use
    Chemical Substances Antihypertensive Agents ; Sodium Chloride Symporter Inhibitors ; Calcium Channel Blockers ; Thiazides ; Gout Suppressants ; Diuretics
    Language English
    Publishing date 2024-03-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-58153-0
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  2. Article ; Online: Diallyl trisulfide (DATS) protects cardiac cells against advanced glycation end-product-induced apoptosis by enhancing FoxO3A-dependent upregulation of miRNA-210.

    Lin, Kuan-Ho / Ng, Shang-Chuan / Lu, Shang-Yeh / Lin, Yueh-Min / Lin, Shu-Hui / Su, Tzu-Cheng / Huang, Chih-Yang / Kuo, Wei-Wen

    The Journal of nutritional biochemistry

    2024  Volume 125, Page(s) 109567

    Abstract: Diabetic cardiomyopathy is a common complication of diabetes, resulting in cardiac hypertrophy and heart failure associated with excessive reactive oxygen species and mitochondria-mediated apoptosis generation. Mitogen-activated protein kinase-c-Jun N- ... ...

    Abstract Diabetic cardiomyopathy is a common complication of diabetes, resulting in cardiac hypertrophy and heart failure associated with excessive reactive oxygen species and mitochondria-mediated apoptosis generation. Mitogen-activated protein kinase-c-Jun N-terminal kinase (MAPK-JNK), regulated by microRNA (miR)-210, affects mitochondrial function and is activated by advanced glycation end-products (AGE) in cardiac cells. Diallyl trisulfide (DATS), an antioxidant in garlic oil, inhibits stress-induced cardiac apoptosis. This study examined whether DATS enhances miR-210 expression to attenuate cardiac apoptosis. We investigated the DATS-mediated attenuation mechanism of AGE-enhanced cardiac apoptosis by modulating miR-210 and its upstream transcriptional regulator, FoxO3a. We found FoxO3a binding sites in the miR-210 promoter region. Our results indicated that DATS treatment inhibited AGE-induced JNK activation, phosphoprotein c-Jun nuclear transactivation, and cardiac apoptosis and reversed the AGE-induced reduction in cardiac miR-210 levels. The luciferase activity after DATS treatment was significantly lower than that of the control and was reversed following AGE treatment. We also showed that FoxO3a, upregulated by DATS treatment, may bind to the miR-210 promoter to enhance its expression and downregulates JNK expression to attenuate AGE-induced cardiac apoptosis. Oral administration of DATS enhanced FoxO3a expression in the heart and reduced diabetes-induced heart apoptosis. Our findings indicate that DATS mediates AGE-induced cardiac cell apoptosis attenuation by promoting FoxO3a nuclear transactivation to enhance miR-210 expression and regulate JNK activation. Our results suggest that DATS can be used as a cardioprotective agent, and miR-210 is a critical regulator in inhibiting diabetic cardiomyopathy.
    MeSH term(s) Humans ; Up-Regulation ; Diabetic Cardiomyopathies/prevention & control ; Glycation End Products, Advanced ; Maillard Reaction ; Sulfides/pharmacology ; Apoptosis ; Cell Line, Tumor ; Mitogen-Activated Protein Kinase Kinases ; MicroRNAs/genetics ; Allyl Compounds
    Chemical Substances diallyl trisulfide (0ZO1U5A3XX) ; Glycation End Products, Advanced ; Sulfides ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; MicroRNAs ; MIRN210 microRNA, human ; Allyl Compounds
    Language English
    Publishing date 2024-01-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1014929-6
    ISSN 1873-4847 ; 0955-2863
    ISSN (online) 1873-4847
    ISSN 0955-2863
    DOI 10.1016/j.jnutbio.2024.109567
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  3. Article: Successful recanalization of the occluded vessel with the assistance of Targeted Adjustable Pharmaceutical Application System (TAPAS) in a patient with an acute deep vein thrombosis and May-Thurner syndrome.

    Lu, Shang-Yeh / Hsu, Chung-Ho

    Radiology case reports

    2018  Volume 13, Issue 6, Page(s) 1256–1258

    Language English
    Publishing date 2018-09-21
    Publishing country Netherlands
    Document type Case Reports
    ZDB-ID 2406300-9
    ISSN 1930-0433
    ISSN 1930-0433
    DOI 10.1016/j.radcr.2018.08.033
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  4. Article: Protective Effects of Statins on Limb and Cardiovascular Outcomes in Patients with Peripheral Artery Disease and End-Stage Renal Disease.

    Lu, Chiung-Ray / Lu, Shang-Yeh / Lin, Shi-Yi / Yip, Hei-Tung / Liu, Chia-Hao / Hsu, Kai-Cheng / Chang, Shih-Sheng

    Acta Cardiologica Sinica

    2023  Volume 39, Issue 5, Page(s) 755–764

    Abstract: Background: Previous studies have reported that statins have inconsistent and marginal cardiovascular (CV) benefits in patients with end-stage renal disease (ESRD). However, whether statins play a secondary preventive role in patients with peripheral ... ...

    Abstract Background: Previous studies have reported that statins have inconsistent and marginal cardiovascular (CV) benefits in patients with end-stage renal disease (ESRD). However, whether statins play a secondary preventive role in patients with peripheral artery disease (PAD) and ESRD remains unclear.
    Objectives: This study aimed to compare the long-term clinical outcomes between statin users and nonusers with PAD and ESRD.
    Methods: This retrospective cohort study assessed the long-term protective effects of statins using data from the National Health Insurance Research Database in Taiwan. Propensity score matching was performed according to sex, age, index year, related comorbidities, and medications. The main outcomes were limb events and major adverse CV events (MACEs).
    Results: The statin user group (n = 4,460) was compared with the propensity score-matched statin nonuser group (n = 4,460). The mean age of the matched patients was 64 years, and 40% of the patients were men. The baseline characteristics of the groups were well-balanced. The overall limb event and MACE rates were not different between the two groups. However, the statin user group had lower rates of limb amputation [adjusted hazard ratio (aHR): 0.85, 95% confidence interval (CI): 0.73-0.99], stroke (aHR: 0.71, 95% CI: 0.62-0.83), CV death (aHR: 0.46, 95% CI: 0.32-0.66), and all-cause death (aHR: 0.45, 95% CI: 0.42-0.48) despite having a higher rate of percutaneous transluminal angioplasty for PAD.
    Conclusions: This population-based retrospective cohort study demonstrated that statin therapy was associated with a lower risk of limb amputation, nonfatal stroke, CV death, and all-cause death in patients with PAD and ESRD.
    Language English
    Publishing date 2023-07-10
    Publishing country China (Republic : 1949- )
    Document type Journal Article
    ZDB-ID 1051394-2
    ISSN 1011-6842
    ISSN 1011-6842
    DOI 10.6515/ACS.202309_39(5).20230118A
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  5. Article ; Online: Platycodi radix aqueous extract salvages doxorubicin-induced senescence by mitochondrial reactive oxygen species reduction in umbilical cord matrix stem cells.

    Lee, Pei-Ying / Sitorus, Maria Angelina / Kuo, Chia-Hua / Tsai, Bruce Chi-Kang / Kuo, Wei-Wen / Lin, Kuan-Ho / Lu, Shang-Yeh / Lin, Yueh-Min / Ho, Tsung-Jung / Huang, Chih-Yang

    Environmental toxicology

    2024  

    Abstract: Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, ... ...

    Abstract Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, derived from Wharton's jelly of the human umbilical cord, has emerged as a promising approach for treating degenerative diseases. Nevertheless, growing evidence indicates that the function of stem cells declines with age, thereby limiting their regenerative capacity. The primary objective in this study is to investigate the beneficial effects of P. radix in senescent stem cells. We conducted experiments to showcase that diminished levels of Lamin B1 and Sox-2, along with an elevation in p21, which serve as indicative markers for the senescent stem cells. Our findings revealed the loss of Lamin B1 and Sox-2, coupled with an increase in p21, in umbilical cord stromal stem cells subjected to a low-dose (0.1 μM) doxorubicin (Dox) stimulation. However, P. radix restored the Dox-damage in the umbilical cord stromal stem cells. P. radix reversed the senescent conditions when the umbilical cord stromal stem cells exposed to Dox-induced reactive oxygen species (ROS) and mitochondrial membrane potential are significantly changed. In Dox-challenged aged umbilical cord stromal stem cells, P. radix reduced senescence, increased longevity, prevented mitochondrial dysfunction and ROS and protected against senescence-associated apoptosis. This study suggests that P. radix might be as a therapeutic and rescue agent for the aging effect in stem cells. Inhibition of cell death, mitochondrial dysfunction and aging-associated ROS with P. radix provides additional insights into the underlying molecular mechanisms.
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1463449-1
    ISSN 1522-7278 ; 1520-4081
    ISSN (online) 1522-7278
    ISSN 1520-4081
    DOI 10.1002/tox.24240
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  6. Article ; Online: Insulin‐like growth factor II receptor alpha overexpression in heart aggravates hyperglycemia‐induced cardiac inflammation and myocardial necrosis

    Lai, Chin‐Hu / Van Thao, Dao / Tsai, Bruce Chi‐Kang / Hsieh, Dennis Jine‐Yuan / Chen, Michael Yu‐Chih / Kuo, Wei‐Wen / Kuo, Chia‐Hua / Lu, Shang‐Yeh / Liao, Shih‐Chieh / Lin, Kuan‐Ho / Huang, Chih‐Yang

    Environmental Toxicology. 2023 Mar., v. 38, no. 3 p.676-684

    2023  

    Abstract: Diabetes‐induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin‐like growth factor II receptor α (IGF‐IIRα) is a cardiac risk factor. In this study, we hypothesized IGF‐IIRα could ... ...

    Abstract Diabetes‐induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin‐like growth factor II receptor α (IGF‐IIRα) is a cardiac risk factor. In this study, we hypothesized IGF‐IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague–Dawley rat model with specific IGF‐IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF‐IIRα in diabetic hearts. The results showed that IGF‐IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro‐inflammatory factors, such as Tumor necrosis factor‐alpha, Interleukin‐6, Cyclooxygenase‐2, Inducible nitric oxide synthase, and Nuclear factor‐kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac‐specific IGF‐IIRα overexpression. Correspondingly, IGF‐IIRα overexpression in the diabetic myocardium also reduced the PI3K‐AKT survival axis and activated mitochondrial‐dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac‐specific IGF‐IIRα overexpression. Overall, all results provid clear evidence that IGF‐IIRα can enhance cardiac damage and is a harmful factor to the heart under high‐blood glucose conditions. However, the pathophysiology of IGF‐IIRα under different stresses and its downstream regulation in the heart still require further research.
    Keywords animal models ; apoptosis ; diabetes ; ecotoxicology ; genetically modified organisms ; glucose ; hyperglycemia ; inducible nitric oxide synthase ; inflammation ; interleukin-6 ; morbidity ; mortality ; myocardium ; necrosis ; pathophysiology ; prostaglandin synthase ; risk factors ; transcription factor NF-kappa B ; tumor necrosis factor-alpha
    Language English
    Dates of publication 2023-03
    Size p. 676-684.
    Publishing place John Wiley & Sons, Inc.
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 1463449-1
    ISSN 1522-7278 ; 1520-4081
    ISSN (online) 1522-7278
    ISSN 1520-4081
    DOI 10.1002/tox.23717
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  7. Article ; Online: Ohwia caudata aqueous extract attenuates doxorubicin‐induced mitochondrial dysfunction in Wharton's jelly‐derived mesenchymal stem cells

    Lee, Pei‐Ying / Tsai, Bruce Chi‐Kang / Sitorus, Maria Angelina / Lin, Pi‐Yu / Lin, Shinn‐Zong / Shih, Cheng‐Yen / Lu, Shang‐Yeh / Lin, Yueh‐Min / Ho, Tsung‐Jung / Huang, Chih‐Yang

    Environmental Toxicology. 2023 Oct., v. 38, no. 10 p.2450-2461

    2023  

    Abstract: Mitochondrial dysfunction has been linked to many diseases, including organ degeneration and cancer. Wharton's jelly‐derived mesenchymal stem cells provide a valuable source for stem cell‐based therapy and represent an emerging therapeutic approach for ... ...

    Abstract Mitochondrial dysfunction has been linked to many diseases, including organ degeneration and cancer. Wharton's jelly‐derived mesenchymal stem cells provide a valuable source for stem cell‐based therapy and represent an emerging therapeutic approach for tissue regeneration. This study focused on screening the senomorphic properties of Ohwia caudata aqueous extract as an emerging strategy for preventing or treating mitochondrial dysfunction in stem cells. Wharton's jelly‐derived mesenchymal stem cells were incubated with 0.1 μM doxorubicin, for 24 h to induce mitochondrial dysfunction. Next, the cells were treated with a series concentration of Ohwia caudata aqueous extract (25, 50, 100, and 200 μg/mL) for another 24 h. In addition, an untreated control group and a doxorubicin‐induced mitochondrial dysfunction positive control group were maintained under the same conditions. Our data showed that Ohwia caudata aqueous extract markedly suppressed doxorubicin‐induced mitochondrial dysfunction by increasing Tid1 and Tom20 expression, decreased reactive oxygen species production, and maintained mitochondrial membrane potential to promote mitochondrial stability. Ohwia caudata aqueous extract retained the stemness of Wharton's jelly‐derived mesenchymal stem cells and reduced the apoptotic rate. These results indicate that Ohwia caudata aqueous extract protects Wharton's jelly‐derived mesenchymal stem cells against doxorubicin‐induced mitochondrial dysfunction and can potentially prevent mitochondrial dysfunction in other cells. This study provides new directions for the medical application of Ohwia caudata.
    Keywords apoptosis ; doxorubicin ; ecotoxicology ; membrane potential ; mitochondria ; mitochondrial membrane ; reactive oxygen species ; therapeutics ; tissue repair
    Language English
    Dates of publication 2023-10
    Size p. 2450-2461.
    Publishing place John Wiley & Sons, Inc.
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 1463449-1
    ISSN 1522-7278 ; 1520-4081
    ISSN (online) 1522-7278
    ISSN 1520-4081
    DOI 10.1002/tox.23880
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  8. Article ; Online: Cardiac-specific overexpression of insulin-like growth factor II receptor-α interferes with the regulation of calcium homeostasis in the heart under hyperglycemic conditions.

    Lu, Shang-Yeh / Tsai, Bruce Chi-Kang / Van Thao, Dao / Lai, Chin-Hu / Chen, Michael Yu-Chih / Kuo, Wei-Wen / Kuo, Chia-Hua / Lin, Kuan-Ho / Hsieh, Dennis Jine-Yuan / Huang, Chih-Yang

    Molecular biology reports

    2023  Volume 50, Issue 5, Page(s) 4329–4338

    Abstract: Background: Diabetic cardiomyopathy is a progressive disease caused by inexplicit mechanisms, and a novel factor, insulin-like growth factor II receptor-α (IGF-IIRα), may contribute to aggravating its pathogenesis. We hypothesized that IGF-IIRα could ... ...

    Abstract Background: Diabetic cardiomyopathy is a progressive disease caused by inexplicit mechanisms, and a novel factor, insulin-like growth factor II receptor-α (IGF-IIRα), may contribute to aggravating its pathogenesis. We hypothesized that IGF-IIRα could intensify diabetic heart injury.
    Methods and results: To demonstrate the potential role of IGF-IIRα in the diabetic heart, we used (SD-TG [IGF-IIRα]) transgenic rat model with cardiac-specific overexpression of IGF-IIRα, along with H9c2 cells, to study the effects of IGF-IIRα in the heart under hyperglycemic conditions. IGF-IIRα was found to remodel calcium homeostasis and intracellular Ca
    Conclusions: Our study reveals the novel role of IGF-IIRα in regulating cardiac intracellular Ca
    MeSH term(s) Rats ; Animals ; Calcium/metabolism ; Insulin-Like Growth Factor II ; Diabetic Cardiomyopathies ; Heart ; Calcium-Binding Proteins/metabolism ; Rats, Transgenic ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/pharmacology ; Homeostasis ; Myocytes, Cardiac/metabolism
    Chemical Substances Calcium (SY7Q814VUP) ; Insulin-Like Growth Factor II (67763-97-7) ; Calcium-Binding Proteins ; Sarcoplasmic Reticulum Calcium-Transporting ATPases (EC 3.6.3.8)
    Language English
    Publishing date 2023-03-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-023-08327-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Ohwia caudata aqueous extract attenuates doxorubicin-induced mitochondrial dysfunction in Wharton's jelly-derived mesenchymal stem cells.

    Lee, Pei-Ying / Tsai, Bruce Chi-Kang / Sitorus, Maria Angelina / Lin, Pi-Yu / Lin, Shinn-Zong / Shih, Cheng-Yen / Lu, Shang-Yeh / Lin, Yueh-Min / Ho, Tsung-Jung / Huang, Chih-Yang

    Environmental toxicology

    2023  Volume 38, Issue 10, Page(s) 2450–2461

    Abstract: Mitochondrial dysfunction has been linked to many diseases, including organ degeneration and cancer. Wharton's jelly-derived mesenchymal stem cells provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for ... ...

    Abstract Mitochondrial dysfunction has been linked to many diseases, including organ degeneration and cancer. Wharton's jelly-derived mesenchymal stem cells provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. This study focused on screening the senomorphic properties of Ohwia caudata aqueous extract as an emerging strategy for preventing or treating mitochondrial dysfunction in stem cells. Wharton's jelly-derived mesenchymal stem cells were incubated with 0.1 μM doxorubicin, for 24 h to induce mitochondrial dysfunction. Next, the cells were treated with a series concentration of Ohwia caudata aqueous extract (25, 50, 100, and 200 μg/mL) for another 24 h. In addition, an untreated control group and a doxorubicin-induced mitochondrial dysfunction positive control group were maintained under the same conditions. Our data showed that Ohwia caudata aqueous extract markedly suppressed doxorubicin-induced mitochondrial dysfunction by increasing Tid1 and Tom20 expression, decreased reactive oxygen species production, and maintained mitochondrial membrane potential to promote mitochondrial stability. Ohwia caudata aqueous extract retained the stemness of Wharton's jelly-derived mesenchymal stem cells and reduced the apoptotic rate. These results indicate that Ohwia caudata aqueous extract protects Wharton's jelly-derived mesenchymal stem cells against doxorubicin-induced mitochondrial dysfunction and can potentially prevent mitochondrial dysfunction in other cells. This study provides new directions for the medical application of Ohwia caudata.
    MeSH term(s) Animals ; Wharton Jelly/metabolism ; Mesenchymal Stem Cells/metabolism ; Doxorubicin/toxicity ; Cells, Cultured ; Mitochondria/metabolism ; Urodela ; Cell Differentiation
    Chemical Substances Doxorubicin (80168379AG)
    Language English
    Publishing date 2023-07-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1463449-1
    ISSN 1522-7278 ; 1520-4081
    ISSN (online) 1522-7278
    ISSN 1520-4081
    DOI 10.1002/tox.23880
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  10. Article ; Online: Angiotensin II prompts heart cell apoptosis via AT1 receptor-augmented phosphatase and tensin homolog and miR-320-3p functions to enhance suppression of the IGF1R-PI3K-AKT survival pathway.

    Lu, Shang-Yeh / Hong, Wei-Zhi / Tsai, Bruce Chi-Kang / Chang, Yu-Chun / Kuo, Chia-Hua / Mhone, Thomas G / Chen, Ray-Jade / Kuo, Wei-Wen / Huang, Chih-Yang

    Journal of hypertension

    2022  Volume 40, Issue 12, Page(s) 2502–2512

    Abstract: Background: Hypertension is a severe public health risk factor worldwide. Elevated angiotensin II (Ang II) produced by the renin-angiotensin-aldosterone system can lead to hypertension and its complications.: Method: In this study, we addressed the ... ...

    Abstract Background: Hypertension is a severe public health risk factor worldwide. Elevated angiotensin II (Ang II) produced by the renin-angiotensin-aldosterone system can lead to hypertension and its complications.
    Method: In this study, we addressed the cardiac-injury effects of Ang II and investigated the signaling mechanism induced by Ang II. Both H9c2 cardiomyoblast cells and neonatal rat cardiomyocytes were exposed to Ang II to observe hypertension-related cardiac apoptosis.
    Results: The results of western blotting revealed that Ang II significantly attenuated the IGF1R-PI3K-AKT pathway via the Ang II-AT1 receptor axis and phosphatase and tensin homolog expression. Furthermore, real-time PCR showed that Ang II also activated miR-320-3p transcription to repress the PI3K-Akt pathway. In the heart tissue of spontaneously hypertensive rats, activation of the IGF1R survival pathway was also reduced compared with that in Wistar-Kyoto rats, especially in aged spontaneously hypertensive rats.
    Conclusion: Hence, we speculate that the Ang II-AT1 receptor axis induces both phosphatase and tensin homolog and miR-320-3p expression to downregulate the IGF1R-PI3K-AKT survival pathway and cause cell apoptosis in the heart.
    MeSH term(s) Rats ; Animals ; Angiotensin II/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphatidylinositol 3-Kinases/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Receptor, Angiotensin, Type 1/metabolism ; Tensins/metabolism ; Rats, Inbred SHR ; Phosphoric Monoester Hydrolases/metabolism ; Phosphoric Monoester Hydrolases/pharmacology ; Rats, Inbred WKY ; Apoptosis ; Myocytes, Cardiac/metabolism ; Hypertension/metabolism ; MicroRNAs/metabolism
    Chemical Substances Angiotensin II (11128-99-7) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Receptor, Angiotensin, Type 1 ; Tensins ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; MicroRNAs ; MIRN320 microRNA, rat
    Language English
    Publishing date 2022-08-31
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0000000000003285
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