Is angiotensin II type 2 receptor a new therapeutic target for cardiovascular disease?

To investigate the effects of PD123319, an antagonist of angiotensin II subtype-2 receptor (AT2R), on the electrophysiological characteristics of the left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHR). A total of twenty-four 10-week-old male SHR were divided into two groups: PD123319 and non-PD123319 groups (n = 12 in each). Twelve 10-week-old Wistar-Kyoto rats served as the control group. Systolic blood pressure, left ventricular mass index (LVMI), ventricular effective refractory period, and ventricular fibrillation threshold were also measured after 8 weeks. I , I, I , and membrane capacitance were measured in the left ventricular myocytes after 8 weeks by whole-cell patch clamp. PD123319 increased LVMI compared with the non-PD123319 group (PD123319 vs. non-PD123319, 3.83 ± 0.11 vs. 3.60 ± 0.19 mg/g; P< 0.01). PD123319 also decreased the ventricular fibrillation threshold compared with the non-PD123319 group (PD123319 vs. non-PD123319, 14.75 ± 0.65 vs. 16.0 ± 0.86 mA; P < 0.01). PD123319 enhanced membrane capacitance compared with the non-PD123319 group (PD123319 vs. non-PD123319, 283.63 ± 5.80 vs. 276.50 ± 4.28 pF; P < 0.05). PD123319 increased the density of I compared with the non-PD123319 group (PD123319 vs. non-PD123319, -6.76 ± 0.48 vs. -6.13 ± 0.30 pA/pF; P< 0.05). PD123319 decreased the density of I compared with the non-PD123319 group (PD123319 vs. non-PD123319, 11.49 ± 0.50 vs. 12.23 ± 0.36 pA/pF; P< 0.05). Long-term treatment with PD123319 worsened the development of myocyte hypertrophy and associated electrophysiological alterations in spontaneously hypertensive rat.

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Long-term treatment of spontaneously hypertensive rats with PD123319 and electrophysiological remodeling of left ventricular myocardium

Xiao

Guan

Long

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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A functional mechanism for a non-coding variant near AGTR2 associated with risk for preterm birth

Wang,

Rossi,

Chen

et al. 2023

BMC Med

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Background Preterm birth (PTB), defined as delivery before 37 gestational weeks, imposes significant public health burdens. A recent maternal genome-wide association study of spontaneous PTB identified a noncoding locus near the angiotensin II receptor type 2 (AGTR2) gene. Genotype-Tissue Expression data revealed that alleles associated with decreased AGTR2 expression in the uterus were linked to an increased risk of PTB and shortened gestational duration. We hypothesized that a causative variant in this locus modifies AGTR2 expression by altering transcription factor (TF) binding. Methods To investigate this hypothesis, we performed bioinformatics analyses and functional characterizations at the implicated locus. Potential causal single nucleotide polymorphisms (SNPs) were prioritized, and allele-dependent binding of TFs was predicted. Reporter assays were employed to assess the enhancer activity of the top PTB-associated non-coding variant, rs7889204, and its impact on TF binding. Results Our analyses revealed that rs7889204, a top PTB-associated non-coding genetic variant is one of the strongest eQTLs for the AGTR2 gene in uterine tissue samples. We observed differential binding of CEBPB (CCAAT enhancer binding protein beta) and HOXA10 (homeobox A10) to the alleles of rs7889204. Reporter assays demonstrated decreased enhancer activity for the rs7889204 risk “C” allele. Conclusion Collectively, these results demonstrate that decreased AGTR2 expression caused by reduced transcription factor binding increases the risk for PTB and suggest that enhancing AGTR2 activity may be a preventative measure in reducing PTB risk.

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Is angiotensin II type 2 receptor a new therapeutic target for cardiovascular disease?

Cited by 2 publications

References 5 publications

Long-term treatment of spontaneously hypertensive rats with PD123319 and electrophysiological remodeling of left ventricular myocardium

Long-term treatment of spontaneously hypertensive rats with PD123319 and electrophysiological remodeling of left ventricular myocardium

A functional mechanism for a non-coding variant near AGTR2 associated with risk for preterm birth

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