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"Pendahuluan –Diabetes Mellitus tipe 2 (DMT2) merupakan sindrom inflamasi progresif dengan peningkatan risiko komplikasi kardiovaskular berupa Atherosclerotic Cardiovascular Disease (ASCVD). Proses thromboinflamasi pada DMT2 ASCVD dikaitkan dengan perubahan pada jumlah serta fungsi leukosit dan trombosit. Rasio leukosit (Neutrophil-Lymphocyte Ratio, Monocyte-Lymphocyte Ratio, Platelet-Lymphocyte Ratio) serta penanda biologis dari netrofil (Peptydil Arginine Deiminase-4), monosit/makrofag (Interleukin-6), dan trombosit (Platelet Glycoprotein 1b-α) dikenali sebagai penanda biologis yang dapat memprediksi perubahan plak stabil dan tidak stabil pada pasien DMT2 ASCVD. Studi ini dilakukan untuk menganalisis hubungan antara klasifikasi pasien DMT2 2 risiko sangat tinggi (Very High Risk / VHR) dan risiko tinggi (High Risk / HR) dan pada pasien DMT2 dengan Acute Coronary Syndrome (ACS) terhadap parameter inflamasi NLR, MLR, PLR, GPIbα, PAD4, dan IL-6. Metodologi – 75 pasien DMT2 ACSVD yang menjalani pengobatan di rawat jalan dan unit gawat darurat Rumah Sakit Pusat Jantung dan Pembuluh Darah Harapan Kita dilibatkan dalam studi ini. Pasien dikategorikan sebagai DMT2 risiko tinggi, DMT2 risiko sangat tinggi, dan DMT2 ACS. Parameter metabolisme dan inflamasi diukur dan dianalisis pada ketiga kelompok DMT2 ASCVD tersebut. Hasil dan Diskusi – Nilai parameter metabolisme kolesterol total dan Low Density Lipoprotein (LDL) serta parameter inflamasi NLR, MLR, PLR, dan IL-6 ditemukan lebih tinggi dan signifikan pada kelompok DMT2 ACS. Nilai Gp1bα ektodomain (Glikokalisin) ditemukan lebih tinggi pada kelompok DMT2 risiko tinggi dan DMT2 risiko sangat tinggi menggambarkan hubungan Gp1bα dan ADAM17 yang terkait dengan keseimbangan pembentukan dan pembersihan trombosit. Nilai PAD4 yang lebih tinggi pada kelompok DMT2 risiko tinggi dan DMT2 risiko sangat tinggi menggambarkan proses perbaikan jaringan dan induksi polarisasi makrofag menjadi fenotip antiinflamasi yang berperan terhadap perbaikan fungsi kardiovaskular. Penelitian ini menunjukkan bahwa nilai NLR dan kolesterol total yang tinggi serta nilai PAD4 yang rendah merupakan prediktor terjadinya keadaan ACS (plak tidak stabil) pada pasien DMT2 ASCVD.

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Introduction – Diabetes Mellitus type 2 (T2DM) is a progressive inflammatory syndrome with an increased risk of cardiovascular complications in the form of Atherosclerotic Cardiovascular Disease (ASCVD). The thromboinflammatory process in T2DM ASCVD is associated with changes in the number and function of leukocytes and platelets. The leukocyte ratio (Neutrophil-Lymphocyte Ratio, Monocyte-Lymphocyte Ratio, Platelet-Lymphocyte Ratio) as well as biological markers of neutrophils (Peptydyl Arginine Deiminase-4), monocytes/macrophages (Interleukin-6), and platelets (Platelet Glycoprotein 1b-α) are recognized as a biological marker that can predict stable and unstable plaque changes in T2DM with ASCVD. This study was conducted to analyze the relationship between the classification of T2DM patients with very high risk (VHR), high risk (HR), and early onset ACS on the inflammatory parameters NLR, MLR, PLR, GPIbα, PAD4, and IL-6.

Methodology – This study included 75 ACSVD T2DM patients being treated at Harapan Kita Heart and Blood Vessel Center Hospital's outpatien and emergency unit. Patients were classified as having high risk T2DM, extremely high risk T2DM, or ACS T2DM. In the three T2DM ASCVD groups, metabolic and inflammatory parameters were evaluated and studied.

Results and Discussion – The metabolic indices total cholesterol and Low Density Lipoprotein (LDL), as well as the inflammatory markers NLR, MLR, PLR, and IL-6, were shown to be greater and significant in the T2DM ACS group. Gp1b ectodomain (Glycocalysin) values were found to be greater in the high risk T2DM and very high risk T2DM groups, demonstrating the relationship between Gp1b and ADAM17, which is associated to platelet production and clearance balance. Higher PAD4 values in the high risk T2DM and very high risk T2DM groups represent tissue repair and the activation of macrophage polarization into an anti-inflammatory phenotype, which contributes to improved cardiovascular function. According to this study, high NLR and total cholesterol levels, as well as low PAD4 levels, are predictors of ACS (unstable plaque) in ASCVD T2DM patients."

"Latar Belakang: Hipertensi merupakan gangguan metabolik yang prevalensinya meningkat secara global dan menjadi penyebab utama morbiditas serta mortalitas. Efektivitas pengobatan antihipertensi, seperti Lisinopril, bervariasi antar populasi, termasuk pada kelompok Melanesia dan non-Melanesia di Indonesia. Perbedaan ini diduga dipengaruhi oleh variasi genetik Renin (rs2887284), ACE-1 (rs4343), Angiotensin-II (rs699) dan epigenetik (ekspresi miR-133 dan miR-155) yang memengaruhi sistem Renin-Angiotensin-Aldosteron (RAAS). Studi sebelumnya belum mengintegrasikan analisis faktor-faktor tersebut secara menyeluruh. Oleh karena itu, penelitian ini bertujuan untuk menganalisis profil genetik, epigenetik, dan biokimia pada pasien hipertensi setelah pemberian Lisinopril di populasi Melanesia dan non-Melanesia.Metode: Sampel plasma dan peripheral blood mononuclear cell (PBMC) didapat dari 79 pasien hipertensi yang terdiri dari 38 populasi Melanesia dan 41 populasi non-Melanesia. Konsentrasi Plasma Renin, ACE-1, dan ANG-II dianalisis dengan menggunakan metode sandwich ELISA. Pemeriksaan SNP Genotyping rs2887284, rs4343, dan rs699 dianalisis dengan qPCR. Pemeriksaan mikroRNA-133 dan miR-155 dianalisis dengan qPCR. Analisis perbedaan antar populasi menggunakan Mann-Whitney Test. Korelasi miR dengan Level ANG-II menggunakan Spearman Test.Hasil: Hasil pemeriksaan ELISA pada Plasma Renin, ACE1, dan ANG-II menunjukkan tidak ada perbedaan konsentrasi Plasma Renin (0,860), ACE1 (0,251), dan ANG-II (0,875) populasi Melanesia dan populasi non-Melanesia. Hasil SNP rs2887284, rs4343, rs699 tidak memiliki perbedaan pada populasi Melanesia dan non-Melanesia. Hasil menunjukkan bahwa miR-133 berhubungan secara signifikan dengan konsentrasi ANG-II baik pada Melanesia dan non-Melanesia (p=<0.001). Terdapat korelasi negatif antara miR-133 dengan ANG-II populasi Melanesia (r=-0,538; p=<0,001) dan Non Melanesia (r=-0,649; p=<0,001).Kesimpulan: Penurunan tekanan darah setelah pemberian Lisinopril lebih rendah pada populasi Melanesia. Polimorfisme rs2887284, rs699, dan rs4343 memengaruhi biomarker RAAS, namun tidak berkorelasi langsung dengan tekanan darah. Ekspresi miR-133 menunjukkan korelasi negatif dengan Angiotensin-II antara populasi Melanesia dan non-Melanesia. Ekspresi miR-155 menunjukkan hubungan berbeda terhadap tekanan darah antara populasi Melanesia dan non-Melanesia.

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Background: Hypertension is a metabolic disorder with an increasing global prevalence and is a leading cause of morbidity and mortality. The effectiveness of antihypertensive therapy, such as Lisinopril, varies among populations, including Melanesians and non-Melanesians in Indonesia. This variability is thought to be influenced by genetic polymorphisms in Renin (rs2887284), ACE-1 (rs4343), and Angiotensinogen (rs699), as well as epigenetic regulation through microRNAs (miR-133 and miR-155), all of which are involved in the Renin-Angiotensin-Aldosterone System (RAAS). Previous studies have not comprehensively integrated these genetic, epigenetic, and biochemical factors. Therefore, this study aims to analyze the genetic, epigenetic, and biochemical profiles in hypertensive patients after Lisinopril administration in Melanesian and non-Melanesian populations.

Methods: Plasma and peripheral blood mononuclear cell (PBMC) samples were collected from 79 hypertensive patients, consisting of 38 Melanesians and 41 non-Melanesians. Plasma concentrations of Renin, ACE-1, and Angiotensin-II were measured using a sandwich ELISA. Analysis of rs2887284, rs4343, rs699 using qPCR. Expression of miR-133 and miR-155 was analyzed using qPCR. Inter-population differences were assessed using the Mann–Whitney U test, and the correlation between microRNA expression and Angiotensin-II levels was analyzed using Spearman's rank correlation test.

Results: ELISA analysis showed no significant differences in the plasma concentrations of Renin (p = 0.860), ACE-1 (p = 0.251), or Angiotensin-II (p = 0.875) between Melanesian and non-Melanesian populations. Result of rs2887284, rs4343, rs699 not significant different between Melanesian dan non-Melanesian. miR-133 expression was significantly negative correlated with Angiotensin-II levels in both populations (p < 0.001), showing a negative correlation in Melanesians (r = –0.538; p < 0.001) and non-Melanesians (r = –0.649; p < 0.001).

Conclusion: The reduction in blood pressure following Lisinopril administration was lower in the Melanesian population. Polymorphisms in rs2887284, rs699, and rs4343 were associated with variations in RAAS biomarkers but did not show a direct correlation with blood pressure reduction. miR-133 expression negatively correlated with Angiotensin-II levels in both populations, while miR-155 showed differential associations with blood pressure between Melanesians and non-Melanesians."