miRNA’ların Hipertansiyon Gelişimindeki Rolü
Özet
Hipertansiyon; tedavi edilmediğinde felç, miyokardiyal enfarktüs ve böbrek hastalıkları gibi ciddi sağlık sorunlarına yol açan küresel bir halk sağlığı problemidir. Genetik ve çevresel faktörlerin rol oynadığı bu karmaşık hastalığın patofizyolojisinde mikroRNA (miRNA) moleküllerinin ekspresyon düzensizlikleri önemli bir yer tutar. Ortalama 22 nükleotit uzunluğunda, protein kodlamayan bu küçük RNA'lar; kononikal veya kononikal olmayan yolaklarla üretilerek hedef mRNA'ların translasyonunu baskılar veya parçalar. İnsan genomunda protein kodlayan genlerin %60'ından fazlası miRNA kontrolü altındadır. Hipertansiyon gelişiminde miRNA'lar; Renin-Anjiyotensin-Aldesteron Sistemi (RAAS), vasküler düz kas hücrelerinin (VSMC) proliferasyon ve migrasyonu, nitrik oksit (NO) sentezi ile endotelyal disfonksiyon ve sempatik sinir sistemi aktivitesi gibi temel mekanizmaları post-transkripsiyonel olarak düzenler. Örneğin, miR-181a ve miR-663 renin ekspresyonunu etkilerken, miR-155 ve miR-200b eNOS seviyelerini baskılayarak vazodilatasyonu bozar. Vücut sıvılarında kararlı şekilde taşınabilen miRNA'lar, hastalıkların prognozunda potansiyel biyobelirteçler sunmanın yanı sıra hipertansiyon ve benzeri poligenik hastalıkların tedavisinde yeni diyagnostik ve terapötik hedefler olarak umut vadetmektedir.
Hypertension is a global public health problem that leads to serious health conditions such as stroke, myocardial infarction, and kidney diseases if left untreated. In the pathophysiology of this complex disease influenced by both genetic and environmental factors, expression irregularities of microRNA (miRNA) molecules play a significant role. These small, non-coding RNAs, averaging 22 nucleotides in length, are produced through canonical or non-canonical pathways and suppress translation or degrade target mRNAs. More than 60% of protein-coding genes in the human genome are under miRNA control. In the development of hypertension, miRNAs post-transcriptionally regulate fundamental mechanisms such as the Renin-Angiotensin-Aldosterone System (RAAS), the proliferation and migration of vascular smooth muscle cells (VSMC), nitric oxide (NO) synthesis leading to endothelial dysfunction, and sympathetic nervous system activity. For instance, miR-181a and miR-663 affect renin expression, while miR-155 and miR-200b suppress eNOS levels to impair vasodilation. Capable of being stably transported in body fluids, miRNAs offer potential biomarkers for disease prognosis and hold promise as novel diagnostic and therapeutic targets for hypertension and similar polygenic diseases.
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