ncRNAs and polyphenols: new therapeutic strategies for hypertension

Figures & data

Figure 1. Schematic classification of polyphenols and their natural sources.

Polyphenols are classified in to two groups of non-flavonoids and flavonoids. Non-flavonoids are subdivided into phenolic acids, lignans and stilbenes. Flavonoids are subdivided into flavonols, flavones, flavanones, flavan-3-ols, anthocyanins and isoflavones.

Figure 2. Summary of the potential mechanisms of action through which polyphenols may affect endothelial health and reduce the risk of hypertension.

Red note refers to the signalling pathways regulated by polyphenols in hypertension.↑denotes increase, ↓denotes decrease.

Table 1. miRNA associated with hypertension

miRNA	Strain/organism/tissue/cell type/disease	Up/Down Regulated	Method of Detection	Regulatory Role	Ref
miR-1	HASMCs/ VSMC/SHRs	Up-regulation	RT-qPCR and western blot analysis	MiR-1 regulates the proliferation of VSMCs by targeting IGF-1	[107]
let-7 g	Human PASMCs and mouse lungs induced by hypoxia	Down-regulation	qPCR-array	let-7 g and LOX-1 inhibit their expression mutually	[108]
miR-21	LEAOD, MCT, hypoxia, hypoxia/Sugen5416, lung and serum of PH patients	Down-regulation	RT-qPCR	MiR-21 lowers blood pressure in spontaneous hypertensive rats	[109]
miR-153	SHR/ Mas/ MCAs/ NT MAs	Up-regulation	RT-qPCR	MiR-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension	[110]
miR-199a-5p	HPASMCs/ HPAECs	Up-regulation	Bioinformatics tools	MiR-199a-5p influences pulmonary artery hypertension via downregulating Smad3	[111]
miR34b	VSMCs	Down-regulation	RT-qPCR	Down-regulated miR-34b is responsible for the elevation of blood pressure	[112]
miR-125a	PAH/ CTEPH	Up-regulation	RT-qPCR	MiR-125a promotes the proliferative phenotype of endothelial cells in pulmonary hypertension	[113]
miR-98	PAECs from PH patients, PAECs under hypoxia and in lung from mice induced by Sugen5416/hypoxia	Down-regulation	Bioinformatics approach using multiple prediction algorithms (miRBase, PicTar, and TargetScan)	PPARγ regulates miR-98 to modulate ET-1 expression and PAEC proliferation	[114]
miR-210	Ovine Uterine Arteries, PAECs induced by hypoxia	Up-regulation	RT-qPCR	MiR-210 modulates the hypoxic human PASMCs by MKP-1	[115]
miR-30c	PAECs from PH patients/ Rat induced by hypoxia and pulmonary arteries (PA) from PH patients	Down-regulation	qPCR-array	MiR-30c contributes to the development of hypoxia pulmonary hypertension	[116]

Table 2. lncRNA associated with hypertension

lnRNA	Strain/organism/tissue/cell type/disease	Up/Down Regulated	Method of Detection	Regulatory Role	Ref
GAS5	VSMC/ EC	Down-regulation	RT-qPCR	GAS5 expression down regulated in HT. knockdown increased SBP and DBP and mean arterial BP (in SHR) retinal neovascularization and capillary leakage, endothelial activation and proliferation	[79]
sONE	BHRs	Down-regulation	qPCR	Lycium Barbarum L. ameliorated HTN, reduced sONE expression and improved eNOS expression compared to high salt diet rats	[103]
749 lncRNAs	SHRs/ normotensive Wistar-Kyoto (WKY) rats	Differential expression between SHR and normotensive rats	Microarray, RNASeq, mRNA trasncrptome analysis	Asb3, Chac2, Pex11b, Sp5	[117]
MALAT1	HUVECs	Up-regulation	RNASeq, Microarray, qPCR	Vessel growth, endothelial cell function	[118]
CDKN2B-AS1	HT patients/ VSMC	Up-regulation	qPCR to test if published 9p21.3 SNPs are associated with BP	Significant difference in genotype freq of the 4 SNPs betw HT and NT. Association betw rs10757274 & rs2383207 (AA) and SBP.	[119]
XR007793	Sprague-Dawley rats/ VSMCs	Up-regulation	qRT-PCR	Kncockdown of XR007793 repress VSMC proliferation & migration. Reduced transcript expression of stat2, lmo2 and irf7.	[76].
H19	PASMCs/ SD rats, C57/BL6 mice/ PAH model	Up-regulation	Discovery meta-analysis, genome-wide SNP genotype	H19-let-7b-AT1R axis contributes to the pathogenesis of PAHT by stimulating PASMCs proliferation	[120]
AK098656	Human plasma/HASMCs	Up-regulation	Microarray, qRT-PCR	Promotes VSMCs proliferation and migration	[77]

Figure 3. Schematic view of regulation of miRNAs and lncRNAs by polyphenols which have been dysregulated in HTN.

lncRNAs and miRNAs regulating the function of RAAS, vascular smooth muscle cells (VSMCs) and the endothelium are depicted. miRNA: microRNA; lncRNA: long non-coding RNA; RAAS: Renin angiotensin aldosterone system; VSMC: vascular smooth muscle cell.

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