Understanding Pathophysiological Complexity of Feline Hypertrophic Cardiomyopathy Using SWATH-MS Plasma Proteomics

TL;DR

This study uses plasma proteomics to identify biomarkers for feline hypertrophic cardiomyopathy, potentially enabling earlier detection and treatment.

Contribution

The study identifies novel plasma biomarkers for feline HCM using SWATH-MS proteomics, revealing similarities to human HCM.

Findings

Forty plasma proteins were found dysregulated in feline HCM, linked to immune and coagulation pathways.

The identified proteomic changes suggest potential for early disease detection and improved treatment outcomes.

Proteomic profiles in feline HCM show similarity to human HCM, supporting cats as a translational model.

Abstract

Feline hypertrophic cardiomyopathy (fHCM) is common cardiac disease, causing higher mortality rates in pet cats. This disease is often asymptomatic, and owners often only realise that their cat has a problem when overt clinical signs develop, which is often too late for any successful management. In this study, we compared the plasma proteome of cats clinically diagnosed with fHCM to healthy cats in an aim to identify possible proteomic dysregulation and understand this complex disease. Proteomic results revealed that there was significant involvement of protein dysregulation in various biological pathways. These dysregulated proteins may be useful in identifying disease onset at a much earlier stage, improving the possibility of treating and not just managing this insidious disease in cats and allowing for more effective monitoring of disease progression in affected cats. This study highlights the value of plasma proteomics in advancing our understanding of fHCM pathology and in identifying potential biomarkers. Another significant finding was that proteomic changes identified in feline HCM had similarity to human HCM and fosters the importance of cats as a human translatory model for studying cardiac diseases.

Establishing plasma biomarkers in the veterinary field has always been a challenge, due to a lack of significant understanding of pathophysiological attributes of disease. Advances in mass spectrometry-based proteomic techniques have improved plasma biomarker discovery in veterinary medicine. Feline hypertrophic cardiomyopathy is the most common cardiac disease in cats and has a complex and not fully elucidated pathophysiology. This study aimed to use SWATH-MS proteomics to identify novel plasma biomarkers for fHCM and to further elucidate disease pathogenesis. Plasma was collected from 20 cats, consisting of healthy controls (n = 10) and a HCM group (n = 10). Cats with fHCM, were diagnosed by echocardiography and disease statuses were determined by a veterinary cardiologist. Undepleted cat plasma samples were digested using FASP and quantitative analysis was performed using DIA-NN. A total of 40 plasma proteins were found to be dysregulated, primarily associated with innate and humoral responses, including complement C7 and C9 and properdin proteins. Other dysregulated proteins were involved in blood coagulation (fibrinogen, fibulin-1), lipid metabolism (apolipoproteins), and inflammation pathways (transthyretin and plasminogen). These findings provide possible biomarkers for fHCM, with the potential to detect disease before clinical signs become evident, which is a significant outcome for fHCM. These proteomic changes suggest critical pathways for earlier intervention and could potentially lead to more effective treatment outcomes. Furthermore, having significant similarity to human disease strengthens the case for using cats as a potential translational model for hHCM.

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