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Fulltext The relationships between thyroid hormones and thyroid-stimulating hormone with lipid profile in euthyroid men

Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Johari MH, Ngah WZ

Int J Med Sci, 2014;11(4):349-55.
PMID: 24578612 DOI: 10.7150/ijms.7104

Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population.
Fulltext Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men

Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Ramli ES, Aminuddin A, et al.

Int J Med Sci, 2014;11(2):151-7.
PMID: 24465160 DOI: 10.7150/ijms.7152

Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men.
Fulltext Thyroid-stimulating hormone is significantly associated with bone health status in men

Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Johari MH, Ngah WZ

Int J Med Sci, 2013;10(7):857-63.
PMID: 23781131 DOI: 10.7150/ijms.5870

Recent studies revealed a novel association between thyroid-stimulating hormone (TSH) and bone health status in healthy male populations. The present study aimed to validate this association and provide new information on the relationship between TSH levels and calcaneal speed of sound (SOS) in men.
Fulltext Smoking and Unstable Plaque in Acute Coronary Syndrome: A Systematic Review of The Role of Matrix Metalloproteinases

Aminuddin A, Cheong SS, Roos NAC, Ugusman A

Int J Med Sci, 2023;20(4):482-492.
PMID: 37057211 DOI: 10.7150/ijms.79889

Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The current review aimed to identify the relationship between smoking and MMPs in patients with ACS. Literature search was conducted from inception until March 2022 in three online databases. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the odds ratio (OR) together with its 95% confidence interval (CI) were determined. A total of 7,843 articles were identified, and only seven studies were included. Four studies investigated the MMP-3 and MMP-9 related genes and found that smokers with certain MMPs genotypes had high risk of ACS. Smoking also increased the MMPs level in patients with ACS compared with non-smokers. Additionally, a meta-analysis of two studies resulted in an increased odd of ACS in smokers with MMP-3 5A allele versus non-smokers with MMP-3 6A6A allele (OR: 15.94, 95% CI: 10.63-23.92; I2 =55%). In conclusion, the current review highlights the role of MMPs in relation to smoking and ACS. The determination of these roles may help in identifying new ACS markers among smokers and the development of drug-targeted treatment.
Nicotine Impairs the Anti-Contractile Function of Perivascular Adipose Tissue by Inhibiting the PPARγ-Adiponectin-AdipoR1 Axis

Abd Rami AZ, Aminuddin A, Hamid AA, Mokhtar MH, Ugusman A

Int J Mol Sci, 2023 Oct 12;24(20).
PMID: 37894791 DOI: 10.3390/ijms242015100

Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ-adiponectin-adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ-adiponectin-adipoR1 axis.
Piper sarmentosum attenuates TNF-α-induced VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells

Ismail SM, Sundar UM, Hui CK, Aminuddin A, Ugusman A

J Taibah Univ Med Sci, 2018 Jun;13(3):225-231.
PMID: 31435328 DOI: 10.1016/j.jtumed.2018.01.003

Objectives: Inflammation plays a key role in the pathogenesis of atherosclerosis. Piper sarmentosum is an herb with antioxidant and anti-atherosclerotic activities. The aim of this study was to evaluate the anti-inflammatory properties of an aqueous extract of P. sarmentosum (AEPS) in human umbilical vein endothelial cells (HUVECs).
Methods: HUVECs were divided into six groups: control, treatment with 10 ng/ml TNF-α, and co-treatment of 10 ng/ml TNF-α with four different concentrations of AEPS (100, 150, 250, and 300 μg/ml) for 24 h. Subsequently, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein expression, U937 monocyte cells adhesion, and nuclear factor-kappaB (NF-κB) p65 expression in HUVECs were measured.
Results: Treatment of TNF-α-stimulated HUVECs with AEPS at different concentrations resulted in decreased VCAM-1 and ICAM-1 protein expression in a dose-dependent manner. Furthermore, AEPS also inhibited TNF-α-stimulated U937 monocyte cells adhesion to HUVECs. In addition, AEPS reduced TNF-α-induced NF-κB p65 expression in a dose-dependent manner.
Conclusions: The results indicated that AEPS suppressed TNF-α-induced VCAM-1 and ICAM-1 expression NF-κB signaling.
Fulltext The association between bone health indicated by calcaneal quantitative ultrasound and metabolic syndrome in Malaysian men

Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Mohd Ramli ES, Aminuddin A, et al.

J Diabetes Metab Disord, 2015;14:9.
PMID: 25789255 DOI: 10.1186/s40200-015-0136-3

BACKGROUND: Previous studies on the relationship between bone health and metabolic syndrome (MS) have revealed heterogeneous results. There are limited studies employing bone quantitative ultrasonometry in evaluating this relationship. This study aimed to determine the relationship between MS and bone health in a group of Malaysian middle-aged and elderly men using bone quantitative ultrasonometry.
METHODS: This cross-sectional study recruited 309 free living Chinese and Malay men aged 40 years and above residing in Klang Valley, Malaysia. Their demographic and anthropometric data were collected. Their calcaneal speed of sound (SOS) was measured using a CM-200 bone ultrasonometer. Their blood was collected for the evaluation of lipid profile, total testosterone and sex hormone-binding globulin. The joint interim MS definition was used for the classification of subjects. Multiple linear regression analysis was used to assess the association between SOS and indicators of MS and the presence of MS, with suitable adjustment for confounders.
RESULTS: There was no significant difference in SOS value between MS and non-MS subjects (p > 0.05). The SOS values among subjects with different MS scores did not differ significantly (p > 0.05). There were no significant associations between SOS values and indicators of MS or the presence of MS (p > 0.05).
CONCLUSIONS: The relationship between bone health and MS is not significant in Malaysian middle-aged and elderly men. A longitudinal study should be conducted to evaluate the association between bone loss and MS to confirm this finding.
Fulltext Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells

Lau CC, Aminuddin A, Chan KM, Paterson IC, Law LM, Ng PY

Life (Basel), 2021 Nov 02;11(11).
PMID: 34833046 DOI: 10.3390/life11111170

Extracellular ATP in the tumor microenvironment exhibits either pro- or antitumor effect via interaction with P2Y receptors, but the intracellular signaling and functional roles of P2Y receptors in oral squamous cell carcinoma (OSCC) are unclear. We aimed to study the effect of ATP on OSCC cell lines and the potential mechanisms involved. Through GEPIA dataset analysis, high expression levels of mRNA encoding P2Y receptors, the ATP-induced G protein-coupled receptors, were associated with better overall patient survival in head and neck squamous cell carcinoma. qPCR analysis showed that the poorly differentiated OSCC SAS cell line, had higher P2RY1 expression level compared to the well-differentiated H103 and H376 cell lines. Western blotting and flow cytometry analyses revealed that ATP phosphorylated ERK and elevated intracellular calcium signaling in all tested cell lines. A significant S-phase cell cycle arrest was observed in SAS, and preincubation with the MEK inhibitor PD0325901 reversed the ATP-induced S-phase arrest. We further demonstrated that ATP induced a slight reduction in cell count and colony formation yet significant apoptosis in SAS. Overall, we postulate that the ATP-induced S-phase arrest effect in SAS cells may be regulated through P2Y receptor-mediated ERK signaling, thus suggesting a potential antitumor effect of ATP via interaction with its distinct profile of P2Y receptors.
Fulltext Profiling of Differentially Expressed MicroRNAs in Human Umbilical Vein Endothelial Cells Exposed to Hyperglycemia via RNA Sequencing

Othman NS, Aminuddin A, Zainal Abidin S, Syafruddin SE, Ahmad MF, Mohd Mokhtar N, et al.

Life (Basel), 2023 May 31;13(6).
PMID: 37374078 DOI: 10.3390/life13061296

Hyperglycemia is the hallmark of diabetes mellitus that results in oxidative stress, apoptosis, and diabetic vascular endothelial dysfunction. An increasing number of microRNAs (miRNAs) have been found to be involved in the pathogenesis of diabetic vascular complications. However, there is a limited number of studies that characterize the miRNA profile of endothelial cells exposed to hyperglycemia. Therefore, this study aims to analyze the miRNA profile of human umbilical-vein endothelial cells (HUVECs) exposed to hyperglycemia. HUVECs were divided into two groups: the control (treated with 5.5 mM glucose) and hyperglycemia (treated with 33.3 mM glucose) groups. RNA sequencing identified 17 differentially expressed miRNAs between the groups (p < 0.05). Of these, 4 miRNAs were upregulated, and 13 miRNAs were downregulated. Two of the most differentially expressed miRNAs (novel miR-1133 and miR-1225) were successfully validated with stem-loop qPCR. Collectively, the findings show that there is a differential expression pattern of miRNAs in HUVEC following exposure to hyperglycemia. These 17 differentially expressed miRNAs are involved in regulating cellular functions and pathways related to oxidative stress and apoptosis that may contribute to diabetic vascular endothelial dysfunction. The findings provide new clues on the role of miRNAs in the development of diabetic vascular endothelial dysfunction, which could be useful in future targeted therapy.
Fulltext The Association between Inflammation and Pulse Wave Velocity in Dyslipidemia: An Evidence-Based Review

Aminuddin A, Lazim MRMLM, Hamid AA, Hui CK, Mohd Yunus MH, Kumar J, et al.

Mediators Inflamm, 2020;2020:4732987.
PMID: 32908450 DOI: 10.1155/2020/4732987

Dyslipidemia is associated with increased arterial stiffness (AS) which may lead to hypertension. Among the methods to assess AS are carotid-femoral and brachial-ankle pulse wave velocity. Dyslipidemia is also known to trigger inflammation. C-reactive protein (CRP) is one of the commonest inflammatory markers measured in the clinical setting. However, the association between inflammation and pulse wave velocity (PWV) in people with dyslipidemia is less studied. Therefore, this review investigated the association between inflammation (as measured by CRP) and PWV in dyslipidemia patients. The search of the literature was conducted via PubMed and Scopus database. The keywords used were "aortic stiffness" OR "arterial stiffness" OR "pulse wave velocity" OR "vascular stiffness" OR "carotid femoral pulse wave velocity" OR "pulse wave analysis" AND "inflammation" OR "c reactive protein" OR "c-reactive protein" OR "high sensitivity c reactive protein" AND "dyslipidemia" OR "hyperlipidemia" OR "hypercholesterolemia" OR "hyperlipoproteinemia" OR "hypertriglyceridemia". The following criteria were used: (1) only full-length original articles published in English language, (2) articles that reported the association between arterial stiffness measured as carotid-femoral PWV (cfPWV) or brachial-ankle PWV (baPWV) and CRP or high-sensitivity CRP, and (3) study involving human subjects. The search identified 957 articles published between 1980 and February 2020. Only eight articles fulfilled the inclusion criteria and were used for data extraction. Five of the studies were cross-sectional studies while another three studies were interventional studies. Seven out of eight papers found a significant positive association between AS and CRP, and the correlation ranged from mild to moderate association (Pearson r = 0.33 to r = 0.624). In conclusion, inflammation is associated with increased PWV in patients with dyslipidemia. This supports the involvement of inflammation in the development of AS in dyslipidemia.
Fulltext Exploring the Relationship of Perivascular Adipose Tissue Inflammation and the Development of Vascular Pathologies

Rami AZA, Hamid AA, Anuar NNM, Aminuddin A, Ugusman A

Mediators Inflamm, 2022;2022:2734321.
PMID: 35177953 DOI: 10.1155/2022/2734321

Initially thought to only provide mechanical support for the underlying blood vessels, perivascular adipose tissue (PVAT) has now emerged as a regulator of vascular function. A healthy PVAT exerts anticontractile and anti-inflammatory actions on the underlying vasculature via the release of adipocytokines such as adiponectin, nitric oxide, and omentin. However, dysfunctional PVAT produces more proinflammatory adipocytokines such as leptin, resistin, interleukin- (IL-) 6, IL-1β, and tumor necrosis factor-alpha, thus inducing an inflammatory response that contributes to the pathogenesis of vascular diseases. In this review, current knowledge on the role of PVAT inflammation in the development of vascular pathologies such as atherosclerosis and hypertension was discussed.
Fulltext Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease

Samah N, Ugusman A, Hamid AA, Sulaiman N, Aminuddin A

Mediators Inflamm, 2023;2023:9715114.
PMID: 37457745 DOI: 10.1155/2023/9715114

Coronary artery disease (CAD) is a caused by atherosclerotic plaque buildup in the coronary arteries that supply blood and oxygen to the heart. Matrix metalloproteinase (MMP) is a family of zinc-dependent endopeptidase that is involved in various stages of atherosclerosis as demonstrated in in vitro and in vivo studies. MMP-2 is associated with both stable and unstable atherosclerotic plaque formation. The current review aimed to identify the role of MMP-2 in atherosclerosis development among CAD patients. Literature search was conducted through four online databases and only studies that were published from 2018 until February 2023 were included. The risk of bias was assessed by using the Newcastle-Ottawa Scale. A total of 10,622 articles were initially identified, and only eight studies that fulfilled the selection criteria were included in this review. The results showed that MMP-2 levels and activity were higher in patients with unstable CAD than those with stable CAD and healthy subjects. There was a significant association between MMP-2 levels and cardiovascular disease with MMP-14 levels, which is a pro-MMP-2 activator. In addition, two single nucleotide polymorphisms of the MMP-2 gene (rs243865 and rs243866) were significantly associated with the development of atherosclerosis. In conclusion, MMP-2 plays a crucial role in the development of atherosclerosis among patients with CAD and could be a potential target for CAD therapy.
Fulltext Vascular Dysfunction among Malaysian Men with Increased BMI: An Indication of Synergistic Effect of Free Testosterone and Inflammation

Aminuddin A, Salamt N, Ahmad Fuad AF, Chin KY, Ugusman A, Soelaiman IN, et al.

Medicina (Kaunas), 2019 Sep 08;55(9).
PMID: 31500378 DOI: 10.3390/medicina55090575

Background and objectives: Obesity is associated with poor vascular function and may lead to future cardiovascular disease (CVD). Obesity is also related to increased inflammation and a low testosterone level. This study was conducted to determine the relationship between inflammation, testosterone level, and vascular function among subjects with an increased body mass index (BMI) and to determine whether both low testosterone and high inflammation have synergistic effects towards vascular dysfunction. Materials and Methods: A total of 303 men aged 40-80 years were recruited from Klang Valley, Malaysia. Their height, weight, blood pressure (BP), lipid, blood glucose level, total testosterone (TT), free testosterone (FT), and C-reactive protein (CRP) were measured. The carotid femoral pulse wave velocity (PWVCF) and augmentation index (AI) were also recorded as markers of vascular function. Results: The mean age of all the subjects was 54.46 ± 9.77 years. Subjects were divided into a low/normal body mass index (BMI) group (BMI < 25 kg/m2; NG, n = 154) and high BMI group (BMI ≥ 25 kg/m2; OG, n = 149). The mean BMI for NG was 22.20 ± 1.94 kg/m2 while for OG was 28.87 ± 3.24 kg/m2 (p < 0.01). The level of TT (OG = 21.13 ± 6.44 versus NG = 16.18 ± 6.16 nmol/L, p < 0.01) and FT (OG = 0.34 ± 0.12 versus NG = 0.39 ± 0.11 nmol/L, p < 0.01) were reduced while the level of CRP [OG = 1.05 (2.80) versus NG = 0.50 (1.50) mmol/L, p = 0.01] was increased in OG compared to NG. PWVCF (OG = 8.55 ± 1.34 versus NG = 8.52 ± 1.42 m/s, p = 0.02) and AI (OG = 16.91% ± 6.00% versus 15.88% ± 5.58%, p < 0.01) were significantly increased in OG after adjustment for other CVD risk factors. The subjects that had both a low FT and an increased CRP had higher AI when compared to those with a high CRP and high FT (p < 0.01). Conclusions: The increased BMI was associated with vascular dysfunction, mediated by a low testosterone level and increased inflammation. Furthermore, having both conditions concurrently lead to higher vascular dysfunction. Weight loss, testosterone supplementation, and the anti-inflammatory agent may be beneficial for men to prevent vascular dysfunction.
Fulltext The changes of aortic stiffness during normal menstrual cycle

Aminuddin, A., Luqman Hakim, A.Z., Chan, S.Y., Nur Elyatulnadia, S., Hul Aamizatkma, H., Nur Shahira Afifa, R., et al.

Medicine & Health, 2018;13(1):117-129.
MyJurnal

Pulse wave velocity (PWV), augmentation index (AI) and finger photoplethysmography fitness index (PPGF) are non-invasive markers of vascular function and may predict future cardiovascular disease (CVD) risk. In women, the changes from both oestrogen and progesterone levels during menstrual cycle may give significant impact on vascular function. Thus, this study was designed to investigate the variation of vascular function during follicular and luteal phase in healthy young women. Twenty-two healthy young women with regular menstrual cycle were recruited. Blood pressure (BP), body mass index (BMI), PWV, AI, PPGF, estradiol (Es) and progesterone (Prog) level were measured during follicular (F) and mid-luteal (L) phase. Data was analyzed via SPSS version 20 and P value < 0.05 was considered to be significant. The mean age of the subjects was 22.73 ± 0.60 years. There was significant variations of estradiol and progesterone levels during menstrual cycle whereby the level of estradiol (EsF = 107.6 ± 52.56 pmol/L vs. EsL = 555.16 ± 152.79 pmol/L, P
Fulltext Four Year Analysis of Helicobacter pylori Infection among Patients with Dyspepsia at Universiti Kebangsaan Malaysia Medical Centre

Alfizah, H., Rizal, A.M., Isa, M.R., Aminuddin, A., Jasmi, A.Y., Ramelah, M.

Medicine & Health, 2010;5(1):13-21.
MyJurnal

Helicobacter pylori has been implicated as an aetiologic agent for type B chronic gastritis, peptic ulcer and gastric cancer. It is considered the most common bacterial infection in the world with approximately 50% of the population being infected. The majority of infected individuals are asymptomatic, with some developing gastritis only. However, chronic infection with H. pylori without antibiotic treatment predisposes infected individuals to the development of gastric cancer. The aim of this study is to determine active H. pylori infection among patients with symptoms of dyspepsia using three combinations of diagnostic methods. In this report, we studied 1,376 consecutive patients who underwent upper gastrointestinal endoscopy at Universiti Kebangsaan Malaysia Medical Center (UKMMC) for dyspepsia from the period January 1999 to December 2002. The classification of patient’s diagnosis was assessed by endoscopic and histological examination. The H. pylori status was determined by rapid urease test, histological examination or H. pylori culture. Presence of H. pylori infection was confirmed in 30.8% of patients with dyspepsia. H. pylori infection was more prevalent in older patients and in males compared to females. Patients with severe gastroduodenal diseases were more commonly infected with H. pylori. There was a significant difference in H. pylori prevalence among the different ethnic groups. Indians had the highest infection rate (45.4%), followed by Chinese (36.8%) and the lowest were seen in Malays (18.3%). This finding on determination of active H. pylori infection among patients with dyspepsia is consistent with serological studies that showed racial differences in H. pylori prevalence. However, the pattern of H. pylori infection does not reflect the prevalence of severe gastroduodenal diseases among different ethnic groups.
Fulltext The assessment of finger photoplethysmography fitness index (PPGF) among young men with cardiovascular disease risk factors: a cross sectional study

Aminuddin, A., Zaiton, Z., Azizah, U., Norizam, S., Nor Anita, M.M.N., Chellappan, K.

Medicine & Health, 2016;11(2):218-231.
MyJurnal

Two new vascular health markers which are derived from finger
photoplethysmography (PPG) waveform have been introduced based on Malaysian
population, namely PPG fitness index (PPGF) and vascular risk prediction index
(VRPI). The objectives of this study were to investigate the associations between
PPGF and other cardiovascular disease (CVD) markers such as carotid femoral pulse
wave velocity (PWVCF), to compare PPGF between those with and without CVD risk
factors and to determine the sensitivity of VRPI in identifying young subjects with
CVD risk factors. A total of 114 men age 20 to 40 yrs with and without CVD risk
factors were recruited. Risk factors included hypertension, smoking, dyslipidemia,
abdominal obesity and family history of premature CVD. Subjects were divided
into healthy, those with one risk factor and those with at least two risk factors. Their
weight, height, peripheral and central blood pressure (BP), PWVCF and PPGF were
measured and the sensitivity of VRPI in predicting subjects with CVD risk factor was
calculated. Data was analyzed via SPSS version 15 and p < 0.05 was considered
significant. The mean age of the subjects was 28.94 ± 4.86 yrs. No differences in
PPGF was observed between groups (p > 0.05). The independent variables for
PPGF were forward pressure (Beta = 0.35, p < 0.01), PWVCF (Beta = -0.26, p < 0.01),
systolic BP (Beta = -0.26, p = 0.04) and height (Beta = 0.24, p < 0.01). The sensitivity
of VRPI was 82.02%. In conclusion, PPGF was correlated to PWVCF and may be a
potential marker of arterial stiffness. In addition, VRPI is sensitive to be used as an
early screening of CVD risk factors.
Fulltext Evaluating the Potential of Plukenetia volubilis Linneo (Sacha Inchi) in Alleviating Cardiovascular Disease Risk Factors: A Mini Review

Abd Rahman IZ, Nor Hisam NS, Aminuddin A, Hamid AA, Kumar J, Ugusman A

Pharmaceuticals (Basel), 2023 Nov 09;16(11).
PMID: 38004453 DOI: 10.3390/ph16111588

Plukenetia volubilis Linneo or Sacha Inchi (SI), a traditional natural remedy indigenous to Peru and Brazil, has garnered global attention due to its exceptional nutritional composition. Its protective effects against various non-communicable diseases, notably cardiovascular disease (CVD), have become a subject of interest in recent research. This comprehensive review summarizes the existing evidence from 15 relevant articles concerning the impact of SI on common CVD risk factors, including dyslipidemia, obesity, diabetes, and hypertension. The relevant articles were derived from comprehensive searches on PubMed, Scopus, Google Scholar, and Web of Science using predefined criteria and keywords related to the topic. Overall, SI demonstrated positive effects in attenuating dyslipidemia, obesity, diabetes, and hypertension. The multifaceted mechanisms responsible for the protective effects of SI against these CVD risk factors are primarily attributed to its antioxidative and anti-inflammatory properties. While preclinical studies dominate the current scientific literature on SI, there are limited clinical trials to corroborate these findings. Therefore, future well-designed, large-scale randomized clinical trials are highly recommended to establish the efficacy of SI and determine its optimal dosage, potential drug and food interactions, and practical integration into preventive strategies and dietary interventions for the high-risk populations.
Endothelial function and dysfunction: Impact of sodium-glucose cotransporter 2 inhibitors

Ugusman A, Kumar J, Aminuddin A

Pharmacol Ther, 2021 08;224:107832.
PMID: 33662450 DOI: 10.1016/j.pharmthera.2021.107832

Diabetes mellitus is associated with endothelial dysfunction that leads to cardiovascular complications. Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrated efficacy in glycemic control in type 2 diabetes patients with positive cardiovascular outcome. Recent research revealed a link between SGLT2 inhibition and improved macro- and microvascular endothelial functions. Mechanisms underlying this phenomenon could be due to the role of SLGT2 in the regulation of endothelial physiology. In this review, current knowledge and hypothesis on the link between SGLT2 and endothelial function were critically appraised and the impact of SGLT2 inhibitors on endothelial dysfunction in pre-clinical and clinical studies was discussed.
Fulltext Effect of increasing heart rate on finger photoplethysmography fitness index (PPGF) in subjects with implanted cardiac pacemakers

Aminuddin A, Tan I, Butlin M, Avolio AP, Kiat H, Barin E, et al.

PLoS One, 2018;13(11):e0207301.
PMID: 30485318 DOI: 10.1371/journal.pone.0207301

Finger photoplethysmography (PPG) is a noninvasive method that measures blood volume changes in the finger. The PPG fitness index (PPGF) has been proposed as an index of vascular risk and vascular aging. The objectives of the study were to determine the effects of heart rate (HR) on the PPGF and to determine whether PPGF is influenced by blood pressure (BP) changes. Twenty subjects (78±8 years, 3 female) with permanent cardiac pacemakers or cardioverter defibrillators were prospectively recruited. HR was changed by pacing, in a random order from 60 to 100 bpm and in 10 bpm increments. At each paced HR, the PPGF was derived from a finger photoplethysmogram. Cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) were derived from the finger arterial pressure waveform. Brachial blood pressure (BP) was measured by the oscillometric method. This study found that as HR was increased from 60 to 100 bpm, brachial diastolic BP, brachial mean BP and CO were significantly increased (p<0.01), whilst the PPGF and SV were significantly decreased (p<0.001). The effects of HR on the PPGF were influenced by BP, with a decreasing HR effect on the PPGF that resulted from a higher BP. In conclusion, HR was a significant confounder for PPGF and it must be taken into account in analyses of PPGF, when there are large changes or differences in the HR. The magnitude of this effect was BP dependent.
Fulltext Antioxidative and anti-inflammatory activities of Polygonum minus: a review of literature

Hamid AA, Aminuddin A, Yunus MHM, Murthy JK, Hui CK, Ugusman A

Rev Cardiovasc Med, 2020 Jun 30;21(2):275-287.
PMID: 32706215 DOI: 10.31083/j.rcm.2020.02.50

Inflammation and oxidative stress are involved in the pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension and ischemic heart disease. Natural products play an important role as nutritional supplements with potential health benefits in cardiovascular diseases. Polygonum minus (PM) is an aromatic plant that is widely used as a flavoring agent in cooking and has been recognized as a plant with various medicinal properties including antioxidative and anti-inflammatory actions. Phytoconstituents found in PM such as phenolic and flavonoid compounds contribute to the plant's antioxidative and anti-inflammatory effects. We conducted this review to systematically identify articles related to the antioxidative and anti-inflammatory activities of PM. A computerized database search was conducted on Ovid MEDLINE, PubMed, Scopus, and ACS publication, from 1946 until May 2020, and the following keywords were used: 'Kesum OR Polygonum minus OR Persicaria minor' AND 'inflammat* OR oxida* OR antioxida*'. A total of 125 articles were obtained. Another eight additional articles were identified through Google Scholar and review articles. Altogether, 17 articles were used for data extraction, comprising 16 articles on antioxidant and one article on anti-inflammatory activity of PM. These studies consist of 14 in vitro studies, one in vivo animal study, one combined in vitro and in vivo study and one combined in vitro and ex vivo study. All the studies reported that PM exhibits antioxidative and anti-inflammatory activities which are most likely attributed to its high phenolic and flavonoid content.

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