کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2005780 | 1541697 | 2016 | 8 صفحه PDF | دانلود رایگان |
• Tow high affinity single-stranded DNA (ssDNA) aptamers (FLC112 and FLC125) against angiotensin II octa-peptide were isolated from an initial large diverse ssDNA pool.
• These ssDNA aptamers can inhibit the proliferative effect of angiotensin II peptide on human aortic vascular smooth muscle cells (HA-VSMCs).
• Anti-angiotensin II ssDNA aptamers showed in vivo activity in Wistar rat through increasing the urine volume and decreasing the blood sodium level.
• These types of aptamers can be regarded as the potent bioactive molecules for using as therapeutic agents in cardiovascular disorders caused by angiotensin II peptide.
Unique features of aptamers have attracted interests for a broad range of applications. Aptamers are able to specifically bind to targets and inhibit their functions. This study, aimed to isolate the high affinity ssDNA aptamers against bio-regulator peptide angiotensin II (Ang II) and investigate their bioactivity in cellular and animal models. To isolate ssDNA aptamers, 12 rounds of affinity chromatography SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure were carried out. The SPR (surface plasmon resonance) and ELONA (enzyme linked oligonucleotide assay) analysis were used to determine the affinity and specificity of aptamers. The ability of selected aptamers to inhibit the proliferative effect of Ang II on human aortic vascular smooth muscle cells (HA-VSMCs) and their performance on Wistar rat urinary system and serum electrolyte levels were investigated. Two full-length aptamers (FLC112 and FLC125) with high affinity of respectively 7.52 ± 2.44E-10 and 5.87 ± 1.3E–9 M were isolated against Ang II. The core regions of these aptamers (CRC112 and CRC125) also showed affinity of 5.33 ± 1.15E-9 and 4.11 ± 1.09E–9 M. In vitro analysis revealed that FLC112 and FLC125 can inhibit the proliferative effect of Ang II on HA-VSMCs (P < 0.05). They also significantly reduced the serum sodium level and increased the urine volume (P < 0.05). The core regions of aptamers did not show high inhibitory potential against Ang II. It can be a spotlight that ssDNA aptamers have high potential for blocking Ang II. In conclusion, it appears that the researches focusing on high affinity and bioactive aptamers may lead to excellent results in blocking Ang II activity.
Journal: Peptides - Volume 82, August 2016, Pages 101–108