Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&amp;#246;ttingen Minipigs and Landrace Pigs

Brenner, Gábor B.; Giricz, Zoltán; Garamvölgyi, Rita; Makkos, András; Onódi, Zsófia; Sayour, Nabil V; Gergely, Tamás G.; Baranyai, Tamás; Petneházy, Örs; Kőrösi, Dénes; Szabó, Gergő P; Vágó, Hajnalka; Dohy, Zsófia; Czimbalmos, Csilla; Merkely, Béla; Boldin-Adamsky, Swetlana; Feinstein, Elena; Horváth, Iván; Ferdinándy, Péter

doi:10.3791/61901

Cited by 11 publications

(9 citation statements)

References 12 publications

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“…To enable the identification of drugs that are possible candidates of drug repurposing for a novel indication in HF, we aimed to identify GPCRs that show significantly different expression in TAC vs. SHAM hearts, as GPCRs are the largest family of targets for already-approved drugs—agonists, antagonists or partial agonists—currently available on the market. Given the general need for increasing translational value and success of preclinical studies in the field of cardiology [ 29 , 30 , 31 , 32 , 33 ], we aimed to conduct a systematic screening of cardiac GPCRs with reduced risk of subjective bias. To this end, we first assessed the cardiac GPCR gene expression both by bulk RNA sequencing and ddPCR, and filtered only for those candidates that (i) were identified by both methods to be significantly differentially expressed in TAC vs. SHAM rat hearts, and (ii) show significant correlation in levels of gene expression measured by both methods.…”

Section: Discussionmentioning

confidence: 99%

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

Sayour,

Tóth,

Nagy

et al. 2023

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Sayour,

Tóth,

Nagy

et al. 2023

IJMS

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“…Increasing studies indicate Göttingen Minipigs as an excellent translational model to study cardiovascular diseases [ 39 , 46 , 47 , 48 , 49 , 50 ], even in consideration of their propensity to develop various disorders of the metabolic syndrome, including obesity, insulin resistance, glucose intolerance, dyslipidemia, and atherosclerosis [ 39 , 51 , 52 , 53 , 54 , 55 , 56 ]. Clinical applications of mesenchymal stem-cell-based tissue engineering are promising due to the specific properties of these cells, i.e., high regenerative capacity, proliferative potential, immunomodulatory activity, and low immunogenicity [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the last decade, miniature swine has been preferred to hybrid pigs for their small size, genetic stability and health status, making them a translational research model that is extremely helpful in biomedical research [ 36 , 37 , 38 ]. In particular, Göttingen Minipigs are widely used in Europe as a translational model in the field of cardiovascular diseases [ 39 , 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation of Vascular Wall Mesenchymal Stem Cells from the Thoracic Aorta of Adult Göttingen Minipigs: A New Protocol for the Simultaneous Endothelial Cell Collection

Bernardini

Mantia

Salaroli

et al. 2023

Animals

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Two main classes of perivascular multipotent populations have been described: the microvascular pericytes and the vascular wall mesenchymal stem cells (VW-MSCs). VW-MSCs are isolated from large vessels in many species and they participate in vascular remodeling together with other cellular components such as endothelial cells. Considering that the Göttingen Minipigs are widely used in Europe as a translational model in the field of cardiovascular diseases, the aim of the present research was to isolate VW-MSCs from the adult aorta of Göttingen Minipigs while preserving and also collecting endothelial cells. The results obtained in the present research demonstrated that this new protocol allows us to obtain a pure population of VW-MSCs and endothelial cells. VW-MSCs from Göttingen Minipigs responded fully to the MSC minima international criteria, being positive to CD105, CD90, and CD44 and negative to CD45 and CD34. Moreover, VW-MSCs presented a differentiative potential towards osteogenic, chondrogenic, and adipogenic lineages. Overall, the present protocol, preserving the viability and phenotypic features of the two isolated populations, opens future possibilities of using minipig VW-MSCs and endothelial cells in in vitro vascular remodeling studies.

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“…No information has been found in minipigs, despite their increasing use in different branches of translational medicine [140][141][142][143]. Further specific studies should be performed characterizing the effects induced by anaesthetic drugs in these animals, also considering that most of them are used as adult.…”

Section: Plos Onementioning

confidence: 99%

How is depth of anaesthesia assessed in experimental pigs? A scoping review

et al. 2023

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Background Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the use of depth of anaesthesia indicators in this species. Methods Medline, Embase and CAB abstract were searched up to September 22nd 2022. No limits were set for time, language and study type. Only original articles of in vivo studies using pigs or minipigs undergoing general anaesthesia were included. The depth of anaesthesia indicators reported in the selected papers were divided in two categories: A, indicators purposely investigated as method to assess depth of anaesthesia; B, indicators reported but not investigated as method to assess depth of anaesthesia. Results Out of 13792 papers found, 105 were included after the screening process. Category A: 17 depth of anaesthesia indicators were found in 19 papers. Studies were conducted using inhalant anaesthetics as the main anaesthetic agent in the majority of the cases (13/19 = 68.4%), while 3/19 (15.8%) used propofol. The most investigated depth of anaesthesia indicators were bispectral index (8/19 = 42.1%) and spectral edge frequency 95% (5/19 = 26.3%). Contrasting results about the specific usefulness of each depth of anaesthesia indicators were reported. Category B: 23 depth of anaesthesia indicators were found in 92 papers. The most reported depth of anaesthesia indicators were: motor response following a stimulus (37/92 = 40.2%), depth of anaesthesia scores (21/92 = 23.3%), bispectral index (16/92 = 17.8%) and spectral edge frequency 95% (9/92 = 9.8%). Conclusion Results highlight the lack of scientifically valid and reliable indicators to ensure adequate depth of anaesthesia in pigs.

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Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs

Abstract: The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF).

Cited by 11 publications

References 12 publications

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

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

Isolation of Vascular Wall Mesenchymal Stem Cells from the Thoracic Aorta of Adult Göttingen Minipigs: A New Protocol for the Simultaneous Endothelial Cell Collection

How is depth of anaesthesia assessed in experimental pigs? A scoping review

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