ORCID Profile
0000-0001-9580-2548
Current Organisation
Baker IDI Heart and Diabetes Institute
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Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.IJCARD.2018.01.077
Abstract: Angiotensin receptor neprilysin inhibitor (ARNi) enhances beneficial natriuretic peptides by inhibiting their breakdown through neprilysin. Although the first-in-class ARNi sacubitril/valsartan (LCZ696) reduced mortality and morbidity in heart failure (HF) with reduced ejection fraction (EF) compared to angiotensin converting enzyme inhibitor (ACEi), mechanistic data on ARNi are scarce. ARNi may be superior to ACEi in attenuating adverse cardiac remodeling and dysfunction post-myocardial infarction (MI). Rats randomized at 1 week post-MI were administered LCZ696 (60 mg/kg, N = 12), the ACEi perindopril (2 mg/kg, N = 11) or vehicle (corn oil, N = 13), orally for 4 weeks. Sham rats received vehicle (corn oil, N = 9). Echocardiography was assessed before and after treatment, prior to invasive hemodynamics using pressure-volume analysis. Hypertrophy and fibrosis was evaluated by histochemical staining, and analysis of myocardial gene and protein expression using real-time quantitative PCR and Western blot. Compared to Sham, MI groups had large infarcts (>40%) and reduced left ventricular (LV) EF. LCZ696 improved LVEF and end systolic pressure-volume relationship compared to perindopril (P < 0.05). LCZ696 but not perindopril reduced lung weight and LV filling pressures post-MI. Reductions in cardiac hypertrophy and fibrosis were similar, however gene expression of hypertrophic markers, ANP and βMHC were reduced with LCZ696 versus perindopril. LCZ696 versus perindopril reduced myocardial TIMP2 gene expression with a trend (P = 0.067) to lowering collagen I. LCZ696 attenuated adverse cardiac remodeling and dysfunction and reduced pulmonary congestion and hypertrophic markers after MI compared to perindopril. This study supports clinical evaluation of ARNi versus ACEi in targeting post-MI cardiac dysfunction and remodeling.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.HLC.2017.12.001
Abstract: Cardiac remodelling is a dynamic process whereby structural and functional changes occur within the heart in response to injury or inflammation. Recent studies have demonstrated reactive oxygen species sensitive MAPK, apoptosis signal-regulating kinase 1 (ASK1) plays a critical role in cardiac remodelling. This study aims to determine the effectiveness of small molecule ASK1 inhibitors on these processes and their therapeutic potential. Neonatal rat cardiac fibroblasts (NCF) were pre-treated with ASK1 inhibitors, G2261818A (G226) and G2358939A (G235), for 2hours before stimulated with 100nM angiotensin II (AngII), 10μM indoxyl sulphate (IS) or 10ng/ml transforming growth factor β Both G226 and G235 dose-dependently attenuated AngII-, IS-, IL-1β- and TNFα-stimulated NCM hypertrophy and hypertrophic gene expression, IS-, AngII- and TGFβ Selective ASK1 inhibition confers anti-hypertrophic and anti-fibrotic effects in cardiac cells, and anti-inflammation in monocytic cells. ASK1 inhibitors may represent novel therapeutic agents to alleviate cardiac remodelling post cardiac injury where hypertrophy, fibrosis and inflammation play critical roles.
Publisher: Elsevier BV
Date: 10-2202
Publisher: Public Library of Science (PLoS)
Date: 06-11-2017
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.TOXLET.2019.03.002
Abstract: Cardiorenal syndrome (CRS) remains a global health burden with a lack of definitive and effective treatment. Protein-bound uremic toxin (PBUT) overload has been identified as a non-traditional risk factor for cardiac, renal and vascular dysfunction due to significant albumin-binding properties, rendering these solutes non-dialyzable upon the state of irreversible kidney dysfunction. Although limited, experimental studies have investigated possible mechanisms in PBUT-mediated cardiac, renal and vascular effects. The ultimate aim is to identify relevant and efficacious targets that may translate beneficial outcomes in disease models and eventually in the clinic. This review will expand on detailed knowledge on mechanisms involved in detrimental effects of PBUT, specifically affecting the heart, kidney and vasculature, and explore potential effective intracellular targets to abolish their effects in CRS initiation and/or progression.
Publisher: Elsevier BV
Date: 05-2015
Publisher: MDPI AG
Date: 18-12-2020
DOI: 10.3390/NCRNA6040050
Abstract: Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression of HCMV disease. HCMV-encoded miRNAs can be detected in blood but have not been sought in saliva. We investigated saliva s les from 32 renal transplant recipients (RTR) and 12 seropositive healthy controls for whom immunological data was available. Five HCMV-encoded miRNAs (miR-UL112-5p, miR-US5-2-3p, miR-UL36, miR-US25-2-3p and miR-UL22A) were sought using primer probe assays. HCMV miRNA species were detected in saliva from 15 RTR and 3 healthy controls, with miR-US5-2-3p most commonly detected. The presence of HCMV miRNAs associated with increased T-cell responses to HCMV IE-1 in RTR, suggesting a link with frequent reactivations of HCMV.
Publisher: Wiley
Date: 20-09-2017
Abstract: Cardiac fibrosis refers to an excessive deposition of extracellular matrix (ECM) in cardiac tissue. Fibrotic tissue is stiffer and less compliant, resulting in subsequent cardiac dysfunction and heart failure. Cardiac fibrosis in the ageing heart may involve activation of fibrogenic signalling and inhibition of anti-fibrotic signalling, leading to an imbalance of ECM turnover. Excessive accumulation of ECM such as collagen in older patients contributes to progressive ventricular dysfunction. Overexpression of collagen is derived from various sources, including higher levels of fibrogenic growth factors, proliferation of fibroblasts and cellular transdifferentiation. These may be triggered by factors, such as oxidative stress, inflammation, hypertension, cellular senescence and cell death, contributing to age-related fibrotic cardiac remodelling. In this review, we will discuss the fibrogenic contributors in age-related cardiac fibrosis, and the potential mechanisms by which fibrogenic processes can be interrupted for therapeutic intent.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Wiley
Date: 13-05-2020
DOI: 10.1111/BPH.15065
Publisher: World Scientific Pub Co Pte Lt
Date: 30-11-2018
DOI: 10.1142/S1793984418410088
Abstract: Cardiovascular disease remains the single highest global cause of death and a significant financial burden on the healthcare system. Despite the advances in medical treatments, the prevalence and mortality for heart failure remain unacceptably high. New approaches are urgently needed to reduce this burden and improve patient outcomes and quality of life. One such promising approach is stem cell therapy, including embryonic stem cells, bone marrow derived stem cells, induced pluripotent stem cells and mesenchymal stem cells. However, the cardiac microenvironment following myocardial infarction poses huge challenges with inflammation, adequate retention, engraftment and functional incorporation all crucial concerns. The lack of cardiac regeneration, cell viability and functional improvement has hindered the success of stem cell therapy in clinical settings. The use of biomaterial scaffolds in conjunction with stem cells has recently been shown to enhance the outcome of stem cell therapy for heart failure and myocardial infarction. This review outlines some of the current challenges in the treatment of heart failure and acute myocardial infarction through improving stem cell therapeutic strategies, as well as the prospect of suitable biomaterial scaffolds to enhance their efficacy and improve patient clinical outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2022
Publisher: World Scientific Pub Co Pte Ltd
Date: 09-2019
DOI: 10.1142/S1793984419410046
Abstract: Stem cell therapy has been tested for cardiac disease therapy for decades. Initially, researchers only considered stem cells’ differentiative ability to repair damaged cardiac tissue. However, studies have now uncovered novel mechanisms contributing to stem cell healing properties to repair injured cardiac tissue, including via paracrine signaling and exosome secretions, leading to amelioration of cardiac remodeling and enhancement of proliferation, regeneration and survival of stem cell-derived cardiac cells. Understanding these underlying mechanisms could help researchers utilize stem cells as a therapeutic strategy for cardiac disease effectively and address the current limitations, mainly surrounding its survival and differentiative ability in the cardiac milieu. This review will discuss the known potential mechanisms underlying the role of stem cells in contributing to and for the treatment of heart diseases.
No related grants have been discovered for Bing Wang.