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The Hypoxic Preconditioning Effect On Senescence Cell Process In Cultured Adipose-Derived Mesenchymal Stem Cells (AMSCs) Nadiar Dwi Nuarisa; I Gde Rurus Suryawan; Andrianto Andrianto
Jurnal Kardiologi Indonesia Vol 39 No 3 (2018): Indonesian Journal of Cardiology: July-September 2018
Publisher : The Indonesian Heart Association

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30701/ijc.v39i3.802

Introduction : Stem cell therapy for myocardial regeneration is expected to increase cardiomyocyte proliferation and trigger neovascularization to improve cardiomyocytes. Mesenchymal Stem Cells (MSCs) are ideal candidates for regenerative medicine and immunotherapy. But low viability of MSCs is a major challenge in this alternative therapy. Therefore, a cytoprotective strategy is needed, one of them is hypoxic preconditioning which can significantly increase survival stem cells after being transplanted. MSCs are known to have a limited life span, after experiencing several splits MSC will enter the senescence process. It is known that hypoxia can also increase cell proliferation and differentiation potential in vitro and in vivo through the role of Octamer-4 (Oct-4) as a regulator of the pluripotency gene. Methods : Experimental laboratory studies (in vitro studies) using human-AMSCs which were given hypoxic preconditioning, observed as a immunocytochemistry. Results : The results showed that hypoxic precondition (1% O2) inhibited the senescence process. It can be seen in the lower expression of senescence in hypoxic conditions at P6, P7, P8, P9, P10 compared to normoxic ((p=0,004, p=0,001, p=0,009, p=0,013, p=0,024. There is a significant difference in the senescence expression of each passage in hypoxic and normoxic conditions with the highest expression at P10. In addition, we also observed AMSCs differentiation through the Oct-4 expression. It is showed that Oct-4 expression were higher in hypoxia compared to normoxia on P7, P8, P9, P10 (p=0,009, p=0,009, p=0,030, p=0,0001). Conclusions : Hypoxic preconditioning have the effect of inhibiting the senescence process on Adipose-derived MSCs (AMSCs) or prolonging their life span. The longer life span of AMSCs is also seen by higher cell differentiation potential from increased expression of Oct-4. However, the mechanism of inhibiting the senescence process in hypoxia in stem cells is still remain unknown. Keywords: human-Adipose derived Mesenchymal Stem Cell Cultures (h-AMSCs), Hypoxic Preconditioning, Senescence cell, Oct-4.

The Role of Ticagrelor in STEMI Fibrinolytic and Its Rationale to Utilize for Indonesian Patients Daniel Tobing; Dafsah Juzar; Achmad Fauzi Yahya; Antonia Anna Lukito; Doni Firman; Sodiqur Rifqi; Abdul Hakim Alkatiri; Rurus Suryawan
Jurnal Kardiologi Indonesia Vol 40 No 4 (2019): Indonesian Journal of Cardiology: October-December 2019
Publisher : The Indonesian Heart Association

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30701/ijc.v40i4.915

Worldwide, ischemic heart disease is the most common cause of death and its frequency is increasing. ST-segment elevation myocardial infarction or STEMIis as form of ischemic heart disease with the highest mortality rate. Based on ESC (European Society of Cardiology) guideline 2017 for STEMI management, reperfusion therapywhich is primary PCI strategy is recommended over fibrinolysis within induced timeframes, but if timely primary PCI cannot be performed after STEMI diagnosis, fibrinolytic therapy is recommended within 12 hours of symptom onset in patients without contraindications. In fibrinolytic therapy, oral aspirin should be given, and Clopidogrel is indicated as an addition to aspirin. Although Clopidogrel is a recommended P2Y12receptor inhibitorin fibrinolytic therapy,PERKI guideline 2018 in ACS management also mention thatswitching to Ticagrelor can be considered in patients whowillundergo PCI treatmentafter fibrinolytic. In PLATO study, patients who have acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke. However, patients who received fibrinolytic therapy within 24 hours before randomization were excluded. WhileinSET-FAST study, Ticagrelor provides more prompt and potent platelet inhibition compared with Clopidogrel in patients undergoing PCI within 24 hours of receiving fibrinolysis for STEMI. TREAT study was conducted to evaluate the safety of ticagrelor in STEMI patients receiving fibrinolytic therapy within 24 hours.TREAT study concluded, at 30 days observation, in patients younger than 75 years with STEMI, delayed administration of Ticagrelor after fibrinolytic therapy was noninferior to Clopidogrel for TIMI major bleeding. Based on the result from PLATO study and preliminary TREAT study result on 30 days, the use of Ticagrelor within 24 hours after fibrinolytic therapy can be considered with comparable safety profile to Clopidogrel. Keywords: STEMI, fibrinolysis, ticagrelor

Association Between Breastfeeding and Nutritional Status In Children With Congenital Heart Disease At Dr. Soetomo General Hospital Safina Fairuz Salwaa; Taufiq Hidayat; I Gde Rurus Suryawan
Syntax Literate Jurnal Ilmiah Indonesia
Publisher : Syntax Corporation

Congenital heart disease (CHD) is a congenital condition caused by a lack of heart development during the fetal stage. There is a notion that children with CHD have low nutritional status due to their condition. Nutritional input, energy requirements, dietary components, and prenatal circumstances impact a person's nutritional status. An analytical observational design with a cross-sectional approach was used in this research. Data were obtained via medical records and questionnaires posed to the patients' guardians who had provided informed consent. The Chi-square test and multivariate logistic regression analysis were used to analyze the data. The study was conducted on 62 subjects. There were 74.19% of subjects with acyanotic CHD and 25.81% with cyanotic CHD. 61.29 % of the subjects were exclusively breastfed for the first six months. The Chi-Square test revealed a relationship between breastfeeding and the nutritional status of children with CHD, with p = 0.0001 (p<0.05). The multivariate logistic regression analysis showed the significance of the type of CHD suffered by the subjects was 0.003 (p<0.05). There is a significant association between breastfeeding for the first six months and the type of CHD suffered by children with their nutritional status at Dr. Soetomo General Hospital.

Correlation Between Diabetes Mellitus and Clinical Outcome of Patients with Acute Coronary Syndrome Underwent Percutaneus Coronary Intervention Therapy in Dr Soetomo Surabaya Hospital Alanna Sari Pratikto; I Gde Rurus Suryawan; Andrianto; Purwo Sri Rejeki
Indonesian Andrology and Biomedical Journal Vol. 1 No. 2 (2020): December
Publisher : Universitas Airlangga

Introduction: Coronary heart diseases continue to be the rising cause of mortality amongst Indonesian population, alongside with the increasing number of diabetic patients. The first line management of ACS is percutaneous coronary intervention (PCI), however previous have shown that diabetic patients have worse outcomes after therapy compared to non-diabetic patients. This study aims to compare the clinical outcomes between acute coronary syndrome (ACS) patients with diabetes and those without diabetes following percutaneus coronary intervention therapy. Methods: This study used cross sectional observational approach collecting records of ACS patients that underwent percutaneous coronary intervention in RSUD Dr Soetomo Surabaya from January 2018 to December 2019. Data regarding a patient’s age, gender, diabetic status, location of lesion, revascularization status, and clinical outcome were collected. Those with missing or incomplete data were excluded from the study. A total of 55 patients were included and analyzed, Results: amongst 55 patients that underwent PCI observed, 23 were diabetic and 32 were non-diabetic. Study has shown that diabetic patients have higher mortality rate compared to those without diabetes (6 patients vs. 1 patient, p=0,072) however based on the result analysis the p value of >0,05 showed no significant relationship between patients’ diabetic status and the clinical outcome following PCI therapy. Study has also shown that diabetic patients are more likely to undergo staged PCI (56,5%), than total revascularization PCI. Conclusion: Study has found that diabetic ACS has a higher mortality rate compared to those without diabetes, however analitycal studies found no significant relationship between the two variables. Further studies should be performed with higher number of patients to accurately investigate the relationship between diabetes melitus and PCI outcomes.

Non-HDL Cholesterol and LDL Cholesterol as Main Risk Factors for Coronary Heart Disease: Meta-Analysis Ravell Hansen Untono; Jusak Nugraha; I. Gde Rurus Suryawan; Andrianto Andrianto
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY Vol 28, No 3 (2022)
Publisher : Indonesian Association of Clinical Pathologist and Medical laboratory

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24293/ijcpml.v28i3.2006

Coronary heart disease is a highly frequent illness in both developed and developing nations. Non-HDL cholesterol (n-HDL-c) and LDL cholesterol (LDL-c) stages are biomarkers that doctors frequently utilize to assess the risk of Coronary Heart Disease (CHD). This study was a systematic review and meta-analysis to assess the association between n-HDL-c and LDL-c as major risk factors for CHD. Cochrane, PubMed, and Science Direct searches were conducted using the keywords "LDL cholesterol," "non-HDL cholesterol," and "coronary heart disease." Any research that describes the analysis of LDL-c and n-HDL-c as key risk factors for CHD and all studies involving patients diagnosed with CHD are included in the literature. A total of seven papers were involved in the qualitative analysis (systematic review), while five studies were included in the quantitative analysis (meta-analysis). The English-language research includes two RCTs, four case-control studies, and one cohort study, with a total of 68,713 individuals. LDL-c parameters were obtained (MD = 8.45; 95 percent CI = 7.03-9.87 p=0.001) and n-HDLc (p=0.001) (MD = 35.57; 95 percent CI = 33.27-37.88). n-HDL-c may be a more significant parameter of CHD risk because it has a higher MD value.

microRNA-1 Induces Transdifferentiation of Peripheral Blood CD34+ Cells into Cardiomyocytes-like Cells Budi Susetio Pikir; Andrianto Andrianto; I Gde Rurus Suryawan; Hanestya Oky Hermawan; Dian Paramita Kartikasari; Primasitha Maharany Harsoyo
The Indonesian Biomedical Journal Vol 14, No 3 (2022)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v14i3.1888

BACKGROUND: Transdifferentiation is a method to provide cells sources for cellular cardiomyoplasty. CD34+ cells are potential cells sources because these cells can differentiate into cardiomyocytes through several mechanisms. MicroRNA (miR-1) is known to have the ability to inhibit the expression of histone deacetylase 4 (HDAC4). HDAC4 is a gene that essentially contributes in cardiomyocytes differentiation. However, the study reporting an evidence that miR-1 can induce transdifferentiation of CD34+ peripheral blood cells into mature cardiomyocytes is limited.METHODS: CD34+ cells were taken from peripheral blood and isolated using a magnetic-activated cell sorting (MACS) method in vitro. Mature mimics of miR-1 were transfected into isolated CD34+ cells and then incubated for 48 hours for quantification of HDAC4 mRNA using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). On the fifth day after miR-1 transfection, cardiomyocyte-like cells were identified based on their morphology and cardiac troponin expression using immunocytochemistry.RESULTS: Transfection of miR-1 in CD34+ isolated cells decreased HDAC4 gene expression by -0.54 fold at second day and caused a significant increase in percentage of cardiac troponin positive cells (median: 31.34; p<0.05) at fifth-day post-transfection. The efficiency of transdifferentiation was 32%. The miR-1 transfection had a significant negative relationship with HDAC4 gene expression (B=-1.000; p=0.001). HDAC4 gene expression had a negative and significant relationship with the percentage of cardiac troponin-positive cells (B=-0.701; p=0.001).CONCLUSION: This study suggests that miR-1 can induce transdifferentiation of peripheral blood CD34+ cells into cardiomyocytes-like cells by decreasing HDAC4 gene expression.KEYWORDS: transdifferentiation, microRNA-1, CD34, cardiomyocyte, HDAC4

Non-HDL Cholesterol and LDL Cholesterol as Main Risk Factors for Coronary Heart Disease: Meta-Analysis Ravell Hansen Untono; Jusak Nugraha; I. Gde Rurus Suryawan; Andrianto Andrianto
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY Vol. 28 No. 3 (2022)
Publisher : Indonesian Association of Clinical Pathologist and Medical laboratory

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24293/ijcpml.v28i3.2006

Coronary heart disease is a highly frequent illness in both developed and developing nations. Non-HDL cholesterol (n-HDL-c) and LDL cholesterol (LDL-c) stages are biomarkers that doctors frequently utilize to assess the risk of Coronary Heart Disease (CHD). This study was a systematic review and meta-analysis to assess the association between n-HDL-c and LDL-c as major risk factors for CHD. Cochrane, PubMed, and Science Direct searches were conducted using the keywords "LDL cholesterol," "non-HDL cholesterol," and "coronary heart disease." Any research that describes the analysis of LDL-c and n-HDL-c as key risk factors for CHD and all studies involving patients diagnosed with CHD are included in the literature. A total of seven papers were involved in the qualitative analysis (systematic review), while five studies were included in the quantitative analysis (meta-analysis). The English-language research includes two RCTs, four case-control studies, and one cohort study, with a total of 68,713 individuals. LDL-c parameters were obtained (MD = 8.45; 95 percent CI = 7.03-9.87 p=0.001) and n-HDLc (p=0.001) (MD = 35.57; 95 percent CI = 33.27-37.88). n-HDL-c may be a more significant parameter of CHD risk because it has a higher MD value.

Losartan Has a Comparable Effect to Human Recombinant ACE2 in Reducing Interleukin-6 (IL-6) Levels on Human Adipocytes Exposed to SARS-CoV-2 Spike Protein Hanestya Oky Hermawan; Meity Ardiana; I Gde Rurus Suryawan; Primasitha Maharany Harsoyo; Muhammad Rafli
The Indonesian Biomedical Journal Vol 15, No 5 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i5.2552

BACKGROUND: High angiotensin-converting enzyme 2 (ACE2) expression in adipocyte cells facilitates the initiation of SARS-CoV-2 infection and triggers a cytokine storm. This finding suggests that obesity is an independent risk factor for the severity of the symptoms caused by COVID-19. The use of cardiovascular medications that focus on ACE2, such as angiotensin II receptor blockers, remains controversial, and their effects on inflammatory cytokine production and ACE2 expression in cells, especially adipocytes, remain inconsistent.METHODS: The human adipocytes were isolated from obese donor subcutaneous adipose tissue and infected with the subunit S1 spike protein from SARS-Cov-2. The adipocytes were later treated with either hrsACE2 or losartan. The levels of ACE2 and inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were measured using enzyme linked immunosorbent assay (ELISA). ACE2 and S1 spike protein binding assays were also performed. RESULTS: ACE2, IL-6, and TNF-α levels were significantly increased in human adipocyte cells infected with SARS-Cov-2 but not IL-1β. There was a statistically significant positive correlation between ACE2 and IL-6 (r=0.878, p<0.001). Administration of losartan and hrsACE2 was shown to reduce ACE2 levels and its binding to the SARS-CoV-2 S1 spike protein, and IL-6 levels were statistically significant, but had no significant effect on IL-1β or TNF-α levels.CONCLUSION: This study shows that the administration of losartan in COVID-19 may not be harmful, but instead has a protective effect similar to that of hrsACE2 in preventing a cytokine storm, especially IL-6.KEYWORDS: obesity, SARS-CoV-2, losartan, IL-6, ACE2

Effects of digoxin in inhibiting ACE2 and SARS-CoV-2 binding for attenuating COVID-19 in human adipocytes Ardiana, Meity; Suryawan, I Gde Rurus; Hermawan, Hanestya Oky; Putri, Primasitha Maharani Harsoyo; Rahma, Safira
Medical Journal of Indonesia Vol. 33 No. 3 (2024): September
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.13181/mji.oa.247273

BACKGROUND Angiotensin-converting enzyme 2 (ACE2) has a role in SARS-CoV-2 incidence, and digoxin is a competitive inhibitor of SARS-CoV-2-ACE2 binding. This study aimed to investigate the effects of digoxin on SARS-CoV-2-ACE2 binding, proinflammatory cytokines, and prothrombotic factors in adipocytes of patients with COVID-19. METHODS This in vitro study used adipocyte cultures, which were divided into negative control, positive control (SARS-CoV-2 S1 spike protein only), SARS-CoV-2 S1 spike protein with digoxin, and SARS-CoV-2 S1 spike protein with human recombinant soluble ACE2 (hrsACE2). Data were analyzed using one-way ANOVA and Pearson correlation. RESULTS SARS-CoV-2 significantly elevated ACE2 and increased interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), tissue factor (TF), and plasminogen activator inhibitor-1 (PAI-1) compared to the negative control group (p<0.001). No SARS-CoV-2-ACE2 binding was detected in SARS-CoV-2 with digoxin and hrsACE2 groups, compared to the positive control group (0 ng/ml versus 0 ng/ml versus 36.33 [1.58] ng/ml, p<0.001). Digoxin significantly decreased IL-6 (48.94 [1.80] ng/ml versus 90.93 [4.29] ng/ml; p<0.001), TNF-α (87.65 [6.88] ng/ml versus 307.95 [57.34] ng/ml; p<0.001), TF (5.33 [0.32] ng/ml versus 6.85 [0.22] ng/ml; p<0.001), and PAI-1 levels (2.92 [0.168] ng/ml versus 4.86 [0.11] ng/ml; p<0.001), compared to positive control group. ACE2 positively correlated with IL-6 (p = 0.004, r = 0.763) and TF (p = 0.004, r = 0.768) but was not correlated with IL-1β, TNF-α, and PAI-1 levels. CONCLUSIONS This study promoted digoxin therapy to prevent cytokine storm and thromboembolism by decreasing IL-6, TNF-α, TF, and PAI-1 in adipocyte cultured models at an early stage of COVID-19.

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