Tesis

Hubungan Antara hsa-miR140-5p, hsa-miR-191-5p, hsa-miR-214-3p dengan hsCRP Pada Aneurisma Aorta Torakalis (AAT) = Relationship between hsa-miR140-5p, hsa-miR-191-5p, hsa-miR- 214-3p with hsCRP on Thoracic Aortic Aneurysm (TAA).

Latar Belakang: Aneurisma aorta merupakan masalah kesehatan global dengan tingkat mortalitas mencapai 80% untuk individu pada usia 65 tahun ke atas. Secara alamiah, aneurisma aorta torakalis (AAT) bersifat asimptomatik, sehingga insiden pasti AAT sulit diperkirakan dan diprediksi lebih besar daripada yang dilaporkan. Perkembangan AAT sangat kompleks karena melibatkan berbagai regulasi molekular. Sitokin proinflamasi seperti high-sensitivity CRP (hsCRP) seringkali digunakan sebagai bioprediktor penyakit kardiovaskular. Di sisi lain, beberapa mikroRNA (miRNA) telah diidentifikasi dan fluktuasinya berkaitan erat dengan individu AAT. Namun, belum ada studi yang melaporkan hubungan antara hsCRP dengan beberapa miRNA seperti hsa-miR140-5p, hsamiR-191-5p, dan hsa-miR-214-3p dan ekspresi gen MTMR4 dan PPP1CB pada pasien AAT. Tujuan: Mengetahui hubungan antara kadar hsa-miR140-5p, hsa-miR-191-5p, dan hsamiR-214-3p, ekspresi gen MTMR4 dan PPP1CB dengan hsCRP dan ukuran AAT pada pasien dengan AAT yang mungkin di pengaruhi oleh variabel antara dan atau variabel perancu. Metode: Penelitian ini merupakan penelitian cross-sectional analitik dengan melibatkan 45 pasien AAT yang belum menjalani terapi intervensi bedah dan / atau non-bedah serta hybrid. Setelah pasien didiagnosis sebagai AAT berdasarkan data rekam medis, pasien yang masuk ke dalam keriteria inklusi kemudian diambil darah untuk dilakukan pemeriksaan laboratorium ekspresi hsa-miR140-5p, hsa-miR-191-5p dan hsa-miR-214-3p, MTMR4, PPP1CB, dan kadar hsCRP di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita. Hasil: Jumlah kejadian AAT menunjukkan mayoritas pasien laki-laki (64,4%) dibandingkan perempuan (35,6%) dengan rerata usia 59 ± 11 tahun. Indeks massa tubuh pasien memiliki nilai median 23,6 kg/m2 (17,5-38,1 kg/m2), rerata tekanan darah 135/64, perokok (35,6%), hiperlipidemia (26,7), diabetes melitus tipe 2 (11,1%), ukuran AAT (mm) (59,8), HsCRP (median 1,9 mg/L), CRP (median 2,0 mg/L), hsa-miR214-3p (median 2,69), hsa-miR-140-5p (median 0,45), hsa-miR191-5p (median 0,26), MTMR4 (median 0,45), dan PPP1CB (median 0,31). Pada multivariate analisis didapatkan hipertensi memiliki hubungan signifikan dengan kejadian AAT. Tidak ada hubungan bermakna antara hsa-miR-140-5p, hsa-miR191-5p, dan hsa-miR214-3p dengan kadar HsCRP. Meskipun Ekspresi MTMR4 dan PPP1CB juga tidak memiliki hubungan bermakna dengan hsCRP, tetapi ekspresi MTMR4 terbukti memiliki hubungan yang bermakna dengan kejadian AAT. Hsa-miR-140-5p memiliki hubungan positif dan signifikan (p < 0,05) dengan ukuran AAT. Kesimpulan: Tidak ditemukan hubungan yang bermakna antara hsa-miR-191, dan hsamiR-214 terhadap perubahan kadar hsCRP maupun ukuran AAT. hsa-mir-140 dan gen MTMR4 memiliki hubungan yang signifikan dengan kejadian AAT. Hipertensi merupakan faktor risiko terkuat untuk terjadinya sporadik AAT.
Kata kunci: Aneurisma Aorta, TAA, hsCRP, miRNA, PPP1CB, MTMR4, biomarker, terapeutik


Background: Aortic aneurysm is a global health issue with a mortality rate reaching 80% for individuals aged 65 and older. Naturally, thoracic aortic aneurysms (TAA) are asymptomatic, making the exact incidence of TAA difficult to estimate and predict, likely being greater than reported. The development of thoracic aortic aneurysm (TAA) is very complex because it involves various molecular regulations. Pro-inflammatory cytokines such as high-sensitivity CRP (hsCRP) are often used as biopredictors of cardiovascular disease. On the other hand, several microRNAs (miRNAs) have been identified, and their fluctuations are closely related to TAA individuals. However, no studies have yet reported the relationship between hsCRP and several miRNAs such as hsa-miR140-5p, hsa-miR-191-5p, and hsa-miR-214-3p, and the expression of the MTMR4 and PPP1CB genes in TAA patients. Objective: To evaluate the relationship among the levels ofhsa-miR140-5p, hsa-miR-191-5p, and hsa-miR-214-3p, as well as the expression of the MTMR4 and PPP1CB genes in connection to hsCRP and AAT size in patients with TAA that may be affected by the variables between and/or confounding variables. Methods: This study is an analytical cross-sectional study involving 45 TAA patients who have not undergone surgical and/or non-surgical and hybrid intervention therapies. After the patients were diagnosed with TAA, each with their respective medical record numbers, blood samples were taken for laboratory examination of the expression of hsa-miR140-5p, hsa-miR- 191-5p, and hsa-miR-214-3p, MTMR4, PPP1CB, and hsCRP levels at National Cardiovascular Center Harapan Kita. Results: The majority of TAA events involved male patients (64.4%) with an average age of 59 ± 11 years. Median BMI was 23.6 kg/m2, mean blood pressure was 135/64, and 35.6% were smokers. Other characteristics included hyperlipidemia (26.7%), type 2 diabetes (11.1%), TAA size (59.5 ± 12.2 mm), hsCRP (median 1.9 mg/L), CRP (median 2.0 mg/L), hsa-miR-214-3p (median 2.69), hsa-miR-140-5p (median 0.45), hsa-miR-191-5p (median 0.26), MTMR4 (median 0.45), and PPP1CB (median 0.31). Hypertension showed a significant link with TAA incidence. No significant relationship was found between hsa-miR-214-3p, hsa-miR-140-5p, and hsa-miR-191-5p with hscrp levels. Although MTMR4 and PPP1CB had no significant relationship with hsCRP, MTMR4 was significantly related to TAA size. hsamiR-140-5p had a positive and significant relationship (p < 0.05) with TAA size. Conclusion: The study found no significant association between hsa-miR-191 and hsa-miR- 214 with hsCRP levels or TAA diameter in patients with TAA. However, a significant relationship was identified between hsa-miR-140 and the MTMR4 gene with the incidence of TAA. Additionally, hypertension was found to be associated with the incidence of TAA.
Key words: Aneurysm, hsCRP, miRNA, therapeutic