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Frontiers in veterinary science2020; 7; 308; doi: 10.3389/fvets.2020.00308

Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis.

Abstract: Endocrinopathic laminitis is pathologically similar to the multi-organ dysfunction and peripheral neuropathy found in human patients with metabolic syndrome. Similarly, endocrinopathic laminitis has been shown to partially result from vascular dysfunction. However, despite extensive research, the pathogenesis of this disease is not well elucidated and laminitis remains without an effective treatment. Here, we sought to identify novel proteins and pathways underlying the development of equine endocrinopathic laminitis. Healthy Standardbred horses ( = 4/group) were either given an electrolyte infusion, or a 48-h euglycemic-hyperinsulinemic clamp. Cardiac and lamellar tissues were analyzed by mass spectrometry (FDR = 0.05). All hyperinsulinemic horses developed laminitis despite being previously healthy. We identified 514 and 709 unique proteins in the cardiac and lamellar proteomes, respectively. In the lamellar tissue, we identified 14 proteins for which their abundance was significantly increased and 13 proteins which were significantly decreased in the hyperinsulinemic group as compared to controls. These results were confirmed via real-time reverse-transcriptase PCR. A STRING analysis of protein-protein interactions revealed that these increased proteins were primarily involved in coagulation and complement cascades, platelet activity, and ribosomal function, while decreased proteins were involved in focal adhesions, spliceosomes, and cell-cell matrices. Novel significant differentially expressed proteins associated with hyperinsulinemia-induced laminitis include talin-1, vinculin, cadherin-13, fibrinogen, alpha-2-macroglobulin, and heat shock protein 90. In contrast, no proteins were found to be significantly differentially expressed in the heart of hyperinsulinemic horses compared to controls. Together, these data indicate that while hyperinsulinemia induced, in part, microvascular damage, complement activation, and ribosomal dysfunction in the lamellae, a similar effect was not seen in the heart. In brief, this proteomic investigation of a unique equine model of hyperinsulinemia identified novel proteins and signaling pathways, which may lead to the discovery of molecular biomarkers and/or therapeutic targets for endocrinopathic laminitis.
Copyright © 2020 Campolo, Frantz, de Laat, Hartson, Furr and Lacombe.
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Publication Date: 2020-06-12 PubMed ID: 32596266PubMed Central: PMC7303262DOI: 10.3389/fvets.2020.00308Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The researchers conducted a thorough investigation of novel proteins and pathways that may be involved in the development of equine endocrinopathic laminitis, a disease similar to human metabolic syndrome lacking effective treatment. In this study, the researchers subjected Standardbred horses to hyperinsulinemia, triggering laminitis, isolated cardiac and lamellar tissues, and then carried out proteomic analysis.

Research Methodology

  • The researchers used healthy Standardbred horses, dividing them into two groups. One group was given an electrolyte infusion, while the other group was subjected to a 48-hour euglycemic-hyperinsulinemic clamp – a procedure intended to induce hyperinsulinemia and subsequently, laminitis.
  • Upon developing laminitis, cardiac and lamellar tissues were extracted from the horses and were analyzed with mass spectrometry – a technique allowing them to identify and quantify proteins in these tissues.

Results of the Study

  • Indeed, all horses that were made hyperinsulinemic developed laminitis. The researchers identified a total of 514 unique proteins in the cardiac proteomes and 709 in the lamellar proteomes.
  • Specially in the lamellar tissue, they found significant changes in the levels of 27 proteins – 14 increased and 13 decreased – associated with the hyperinsulinemic state.
  • Through a STRING analysis, a method to understand protein-protein interactions, it was found that increased proteins were mainly linked to coagulation and complement cascades, platelet activity, and ribosomal function. On the other hand, the decreased proteins were involved in spliceosomes, focal adhesions, and cell-cell matrices.
  • The new significant proteins associated with hyperinsulinemia-induced laminitis were identified, which include talin-1, vinculin, cadherin-13, fibrinogen, alpha-2-macroglobulin, and heat shock protein 90.
  • Interestingly, no significant protein expression difference was noted in the heart tissues of the hyperinsulinemic horses compared to the control group.

Conclusion and Implications

  • The research underscored the pathological impact of hyperinsulinemia on horse lamellae, leading to microvascular damage, complement activation, and ribosomal dysfunction, while a similar effect was not observed in the heart.
  • These newly identified proteins and signaling pathways in the lamellar tissue under hyperinsulinemia could potentially be employed as molecular biomarkers for early detection or as therapeutic targets for the treatment of endocrinopathic laminitis.

Cite This Article

APA
Campolo A, Frantz MW, de Laat MA, Hartson SD, Furr MO, Lacombe VA. (2020). Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis. Front Vet Sci, 7, 308. https://doi.org/10.3389/fvets.2020.00308

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 7
Pages: 308
PII: 308

Researcher Affiliations

Campolo, Allison
  • Department of Biochemistry and Molecular Biology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
Frantz, Matthew W
  • Department of Biochemistry and Molecular Biology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
de Laat, Melody A
  • Department of Biochemistry and Molecular Biology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
  • Biosciences, Queensland University of Technology, Brisbane, QLD, Australia.
Hartson, Steven D
  • Department of Biochemistry and Molecular Biology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
Furr, Martin O
  • Department of Biochemistry and Molecular Biology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
Lacombe, Véronique A
  • Department of Biochemistry and Molecular Biology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.

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Citations

This article has been cited 1 times.
  1. Espinosa-López EM, Ortiz-Guisado B, Diez de Castro E, Durham A, Aguilera-Tejero E, Gómez-Baena G. Quantitative proteomics unveils potential plasma biomarkers and provides insights into the pathophysiological mechanisms underlying equine metabolic syndrome. BMC Vet Res 2025 Jul 2;21(1):425.
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