Paul Chan

Paul Chan
Taipei Medical University | TMU

About

186
Publications
16,006
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4,756
Citations
Citations since 2016
58 Research Items
2055 Citations
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300

Publications

Publications (186)
Article
Introduction: Sulfonylureas have been the standard second-line treatment after failure of metformin monotherapy in patients with type 2 diabetes (T2D) but they are becoming less popular as the newer glucose lowering agents have relatively lower risk of hypoglycemia and some of them have been shown to reduce cardiovascular and renal events. Gliclaz...
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Purpose: With increase of population aging, the prevalence of atherosclerotic cardiovascular disease (ASCVD) and elevated serum thyroid stimulating hormone (TSH) in elderly is increasing. High TSH level was reported to be associated with ASCVD and CVD mortality; however, few are studied in Chinese population, especially in the elderly. This study...
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Aims Lung type 2 alveolar cells, by secreting surfactant to lower surface tension, contribute to enhance lung compliance. Stretching, as a result of lung expansion, triggers type 1 alveolar cell to release ATP, which in turn stimulates Ca²⁺-dependent surfactant secretion by neighboring type 2 cells. In this report, we studied ATP-triggered Ca²⁺ sig...
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Background The endothelium is essential for maintaining vascular physiological homeostasis and the endothelial injury leads to the neointimal hyperplasia because of the excessive proliferation of vascular smooth muscle cells. Endothelial Foxp1 (forkhead box P1) has been shown to control endothelial cell (EC) proliferation and migration in vitro. Ho...
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Background Hyperhomocysteinemia (HHcy) and abdominal obesity are risk factors for metabolic syndrome (MetS) and death from cardiovascular disease (CVD). Recent studies have shown a correlation between HHcy and abdominal obesity, suggesting that they may have a combined effect on the risk of MetS and CVD mortality. However, this suspicion remains to...
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Introduction Inclisiran is a small interfering RNA that inhibits hepatic production of proprotein convertase subtilisin/kexin type 9 (PCSK9) which results in reduction of circulating low-density lipoprotein cholesterol (LDL-C). It can be used alone or in combination with statins or other lipid-lowering therapy. Areas covered In this article we rev...
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Context Various herbal medicines are thought to be useful in the management of cardiometabolic disease and its risk factors. Ganoderma lucidum (Curtis) P. Karst. (Ganodermataceae), also known as Lingzhi, has received considerable attention for various indications, including some related to the prevention and treatment of cardiovascular and metaboli...
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Introduction Type 2 diabetes (T2D) is increasingly prevalent and associated with increased risk for cardiovascular and renal disease. After lifestyle modification, metformin is usually the first-line pharmacotherapy and sulfonylureas are traditionally added after metformin failure. However, with newer glucose lowering drugs that may have less risk...
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Background and aims: Coronary artery disease (CAD) is usually caused by atherosclerosis, which is associated with general obesity and stronger associations with localized ectopic fat depots have been reported. We measured body ectopic fat distribution in Chinese patients to determine the association with coronary artery atherosclerosis (CA). Meth...
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Introduction Type 2 diabetes (T2D) is a progressive condition and sequential additions of therapy are usually required to maintain glycemic control. The options for glucose lowering therapies have increased considerably in recent years. Fixed-dose combinations such as alogliptin with pioglitazone provide a convenient choice which can improve medica...
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In this report we examined the effects of lidocaine on Ca2+ homeostasis of neuronal cells using microfluorimetric measurement of cytosolic Ca2+ with fura 2 as probe. In mouse neuroblastoma N2A cells, 10 mM lidocaine caused Ca2+ release from the cyclopiazonic acid (CPA)-dischargeable pool and abolished ATP-triggered Ca2+ release. Lidocaine-triggered...
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Objective: An association of atrial fibrillation (AF) with epicardial fat volume (EFV) varied in different ethnic groups. We evaluated the AF-related risk factors and its association with pericardial fat in Chinese patients. Methods: Patients referred for coronary computed tomography angiography (CCTA) in Shanghai East Hospital during 2012 to 20...
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Ca2+-sensing receptors (CaSR), activated by elevated concentrations of extracellular Ca2+, have been known to regulate functions of thyroid cells, neurons, and endothelial cells (EC). In this report, we studied CaSR-mediated Ca2+ influx in mouse cerebral microvascular EC (bEND.3 cells). Cytosolic free Ca2+ concentration and Mn2+ influx were measure...
Article
The choice of lipid-modifying treatment is largely based on the absolute level of cardiovascular risk and baseline lipid profile. Statins are the first-line treatment for most patients requiring reduction of low-density-lipoprotein cholesterol (LDL-C) and ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors can be added to reach L...
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Aims: Pathological cardiac fibrosis and hypertrophy are common features of left ventricular remodeling that often progress to heart failure (HF). Endothelial cells (ECs) are the most abundant non-myocyte cells in adult mouse heart. Simvastatin, a strong inducer of Krüppel-like Factor 2 (Klf2) in ECs, ameliorates pressure overload induced maladaptiv...
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Introduction Statins are the first-line treatment to reduce cardiovascular (CV) events, mainly by reducing low-density-lipoprotein cholesterol (LDL-C), but many patients need additional treatments to reach the current lipid goals. Areas covered Herein, the authors review the published literature on the efficacy and safety of the therapies that are...
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Introduction: Postprandial hyperlipidemia is a common feature of the atherogenic dyslipidemia in patients with type 2 diabetes. Quantification of this with oral fat tolerance tests is not used routinely in clinical practice and abnormal postprandial lipids are usually inferred from non-fasting plasma triglyceride levels. Identifying excessive postp...
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Introduction: Reduction of low-density-lipoprotein cholesterol (LDL-C) and other apolipoprotein B (apoB)-containing lipoproteins reduces cardiovascular (CV) events and greater reductions have greater benefits. Current lipid treatments cannot always achieve desirable LDL-C targets and additional or alternative treatments are often needed. Areas cove...
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Tannic acid (TA) is a polyphenol compound present in wines and many beverages. Although previous works have shown that TA could cause vasodilation in an endothelial cell (EC)-dependent manner, there is hitherto no report showing whether TA could raise EC cytosolic Ca²⁺ concentration. In this work we examined the effects of TA on cytosolic Ca²⁺ of m...
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Introduction: The prevalence of obesity is increasing worldwide and associated conditions, particularly type 2 diabetes mellitus (T2DM), also show increasing prevalence. Lifestyle intervention should be the first line of management for obesity but additional pharmacotherapy is often required and bariatric surgery is appropriate in more severe cases...
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Quercetin is a flavonol polyphenol widely found in many vegetables, grains and fruits. Quercetin has been shown to inhibit proliferation and invasion of various glioma cells, and is regarded as a potential anticancer agent against glioma. However, whether and how this drug could affect brain blood vessels and endothelial cells are less understood....
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Rationale: Endothelial dysfunction results in sustained and chronic vascular inflammation which is central to atherosclerotic diseases. However, transcriptional regulation of vascular endothelial inflammation has not been well clarified. Objective: This study aims to explore forkhead box P transcription factor 1 (Foxp1) in regulation of endothel...
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Ca²⁺-sensing receptors (CaSR) are G protein-coupled receptors which are activated by a rise in extracellular Ca²⁺. CaSR activation has been known to inhibit parathyroid hormone release and stimulate calcitonin release from parathyroid glands and thyroid parafollicular C cells, respectively. The roles of CaSR in other cell types including endothelia...
Article
Background: Pathological cardiac fibrosis and hypertrophy, the common features of left ventricular remodeling, often progress towards heart failure. Forkhead box transcription factor P1 (Foxp1) in endothelial cells (ECs) has been shown to play an important role in heart development, however, the effect of EC-Foxp1 on pathological cardiac remodelin...
Article
Objective— Transcription factor GATA (GATA zinc finger transcription factor family)-6 is highly expressed in vessels and rapidly downregulated in balloon-injured carotid arteries and viral delivery of GATA-6 to the vessels limited the neointimal formation, however, little is known about its cell-specific regulation of in vivo vascular smooth muscle...
Article
Introduction: Cardiovascular disease is a major cause of morbidity and mortality throughout the world and hypercholesterolemia is one of the key risk factors. Statins are the first line treatment to reduce atherogenic lipids and there is substantial and robust evidence with atorvastatin for reduction of cardiovascular events and mortality. Ezetimi...
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Introduction: Statins are the first line of therapy to reduce low-density lipoprotein cholesterol (LDL-C) in order to decrease cardiovascular events. Pitavastatin is the latest statin to be introduced to the market. Areas covered: In this article, the authors review the efficacy, safety, and tolerability of pitavastatin. The authors also review a r...
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Introduction: Metformin is recommended as first line treatment for type 2 diabetes (T2D) by all major diabetes guidelines. With appropriate usage it is safe and effective overall, but its efficacy and tolerability show considerable variation between individuals. It is a substrate for several drug transporters and polymorphisms in these transporter...
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Background Circulating endothelial‐derived microparticles (EMPs) are reported to be increased in acute coronary syndrome (ACS). However, it remains unclear whether EMPs from dysfunctional endothelium participate in the initiation and progression of ACS and what the underlying mechanisms might be. Methods Plasma EMPs were measured in 22 patients wi...
Article
A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation (EDR) and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylchol...
Data
Supplementary methods, figures and tables.
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We determined the prevalence of hypertension, medication usage and attainment of blood pressure goals in older (≥65 to <80 years and ≥80 years) urban community-dwelling Chinese subjects. Data were obtained in 3950 subjects (mean age 72.0 years, 1745 male) including 609 subjects aged ≥80 years in the Shanghai Elderly Cardiovascular Health Study (SHE...
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Introduction: Evolocumab is a fully human monoclonal immunoglobulin G2 directed against human proprotein convertase subtilisin/kexin type 9 (PCSK9). It is administered by subcutaneous injection every 2 weeks or once monthly. Area covered: Herein, the authors discuss the rationale for inhibiting PCSK9 and describe the pharmacodynamics, pharmacokinet...
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Introduction: Alirocumab is a human monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) that is administered by subcutaneous injection every 2 weeks. Area covered: Herein, the authors discuss the background to inhibition of PCSK9 and the pharmacodynamics, pharmacokinetics and clinical trials with alirocumab. Alirocu...
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The article by Bays et al. in this issue of the journal describes an interesting analysis of the weight loss dependent and weight loss independent mechanisms for the improvement in cardiometabolic parameters with high dose liraglutide in 3 studies in overweight and obese adults with or without type 2 diabetes mellitus (T2DM) and with or without obs...
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Eicosapentaenoic acid (EPA), an omega-3 fatty acid abundant in fish oil, protects endothelial cells (EC) from lipotoxicity and triggers EC NO release. The latter is related to an elevation of cytosolic Ca2+. Although EPA has been shown to cause human EC cytosolic Ca2+ elevation, the mechanism is unclear. Microfluorimetric imaging was used here to m...
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Introduction: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest class of drugs to be introduced for the treatment of type 2 diabetes mellitus. These drugs improve glycemic control by increasing urinary glucose excretion and exert additional benefits of weight loss and blood pressure reductions. Areas covered: This review outlines th...
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Rationale: Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367cluster in angiogenesis and tumors has not yet been fully evaluated. Objective: To investigate the...
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Lipid levels are increasing in all age groups in the Chinese population, but the use of statin treatment in the elderly is not well documented. We examined serum lipids, statin usage and achievement of lipid goals in 3950 subjects aged ≥65 years. Established CVD was present in 7.77% of participants and increased CVD risk was common. Elevated LDL-C...
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Cells switch to anaerobic glycolysis when there is a lack of oxygen during brain ischemia. Extracellular pH thus drops and such acidosis causes neuronal cell death. The fate of astrocytes, mechanical and functional partners of neurons, in acidosis is less studied. In this report we investigated the signaling in acidosis-challenged rat cortical astr...
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Introduction: Obesity is a worldwide problem predisposing to type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, cancer and other comorbidities. Lifestyle modification is the first line intervention but adjunctive pharmacotherapy is often required. The GLP-1 receptor agonists (GLP-1RAs) were developed primarily for T2DM and they...
Article
Tanshinone IIA is the main effective component of Salvia miltiorrhiza, known as "Danshen," which has been used in many therapeutic remedies in traditional Chinese medicine. However, the direct effects of tanshinone IIA on vascular endothelial cells have not yet been fully described. In the present study, we demonstrated that tanshinone IIA increase...
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Obesity is usually considered to predispose to atherosclerotic cardiovascular disease (ASCVD) but milder degrees of obesity or overweight may be protective in some elderly populations. We examined the relationships between general and abdominal obesity indices with ASCVD and its risk factors in elderly (aged ≥65 years) Shanghai community residents...
Article
Introduction: The increasing prevalence of type 2 diabetes mellitus (T2DM) and the eventual need for multiple medications in most patients stimulated the development of new drug classes to reduce plasma glucose levels. The GLP-1 receptor agonists (GLP-1RAs) are established as an option for treatment of T2DM after metformin. They are also effective...
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Cutaneous flushing with niacin varies between individuals and is substantially reduced by concomitant laropiprant. We investigated associations between baseline phenotypes and selected genotypes and flushing symptoms with niacin/laropiprant combination. Flushing symptoms were quantified in 196 Chinese dyslipidaemic patients treated with niacin/laro...
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Release of nitric oxide (NO) is triggered by a rise in endothelial cell (EC) cytosolic Ca(2+) concentration ([Ca(2+)]i) and is of prime importance in vascular tone regulation as NO relaxes vascular smooth muscle. Agonists could stimulate EC [Ca(2+)]i elevation by triggering Ca(2+) influx via plasma membrane ion channels, one of which is the store-o...
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Giant coronary artery aneurysm with a fistula is a rare condition. The presence of a giant aneurysm imposes considerable health risks. We report a case of a 67-year-old woman who presented with frequent ventricular premature contractions caused by a giant coronary aneurysm arising from a branch of the left anterior descending coronary artery that h...
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Astrocytes have multiple functions such as provision of nourishment and mechanical support to the nervous system, helping to clear extracellular metabolites of neurons and modulating synaptic transmission by releasing gliotransmitters. In excitable cells, voltage-gated K(+) (Kv) channels serve to repolarize during action potentials. Astrocytes are...
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Introduction: The fibrates have been used for many years to treat dyslipidemias and have also recently been shown to have anti-inflammatory effects. They are relatively weak PPAR-α agonists and do have some adverse effects. Novel compounds are in development, which are selective PPAR modulators (SPPARMs) and have more potent PPAR-α agonist activit...
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Background Astrocytes do not only maintain homeostasis of the extracellular milieu of the neurons, but also play an active role in modulating synaptic transmission. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for lipotoxicity. Activation of astrocytes by PA has been shown to cause neuronal...
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We conducted this study to investigate how an exercise program affects the risk components of metabolic syndrome (MS), serum interleukin (IL)-6 levels, and exercise capacity in postmenopausal women. A randomized clinical trial design was used. Women in an exercise group participated in a treadmill-exercise program for 12 weeks, whereas women in a c...
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The present study investigated the merit of ginseng in the improvement of heart failure in diabetic rats and the role of peroxisome proliferator-activated receptors δ (PPAR δ ). We used streptozotocin-induced diabetic rat (STZ-rat) to screen the effects of ginseng on cardiac performance and PPAR δ expression. Changes of body weight, water intake, a...
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Imperatorin is a naturally ocurring furocoumarin compound isolated from plants such as Angelica archangelica and Cnidium monnieri. It has multiple pharmacological effects including anticonvulsant effects. Here we determined the effects of imperatorin on voltage-gated Na(+) channels (VGSC) using whole-cell patch clamp techniques in differentiated ne...
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Background Strong P2X7 receptor (P2X7R) activation causes Ca2+ overload and consequent cell death. We previously showed that depletion of Ca2+ stores and endoplasmic reticulum (ER) stress in differentiated NG108-15 neuronal cells contributed to P2X7R-mediated cytotoxicity. In this work, we assessed whether taurine (2-aminoethanesulfonic acid) could...