Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled
Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced
Cardiac Dysfunction
Establishing the Hungarian Center of Excellence for Molecular Medicine in partnership
with EMBL(739593) Támogató: Horizon 2020
(LP-2021-14)
(RRF-2.3.1-21-2022-00003)
(NVKP-16-1-2016-0017 National Heart Program) Támogató: NKFIH
(2020-4.1.1.-TKP2020)
(TKP2021-EGA-23) Támogató: Innovációs és Technológiai Minisztérium
National Research, Development and Innovation Office (NKFIH) of Hungary(K134939)
National Research, Development and Innovation Office (NKFIH) of Hungary(FK134751)
János Bolyai Research Scholarship of the Hungarian Academy of Sciences
(ÚNKP-22-5-SE-20)
Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009)
Támogató: EFOP-VEKOP
(European Union’s Horizon 2020 Research and Innovation (101007931))
The identification of novel drug targets is needed to improve the outcomes of heart
failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of
targets for already approved drugs, thus providing an opportunity for drug repurposing.
Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs
via droplet digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of
left ventricular pressure-overload; (ii) to compare RNAseq findings with those of
ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF.
Male Wistar rats subjected to transverse aortic constriction (TAC, n = 5) showed significant
systolic dysfunction vs. sham operated animals (SHAM, n = 5) via echocardiography.
In TAC vs. SHAM hearts, RNAseq identified 69, and ddPCR identified 27 significantly
differentially expressed GPCR mRNAs, 8 of which were identified using both methods,
thus showing a correlation between the two methods. Of these, Prostaglandin-F2α-receptor
(Ptgfr) was further investigated and localized on cardiomyocytes and fibroblasts in
murine hearts via RNA-Scope. Antagonizing Ptgfr via AL-8810 reverted angiotensin-II-induced
cardiomyocyte hypertrophy in vitro. In conclusion, using ddPCR as a novel screening
method, we were able to identify GPCR targets in HF. We also show that the antagonism
of Ptgfr could be a novel target in HF by alleviating cardiomyocyte hypertrophy.