Proteomic profiling of left atrial strain provides new plasma proteins that may be associated with the development or early complications of cardiovascular disease (CVD)

Background Left atrial (LA) function has a significant impact on cardiovascular diseases (CVD). In recent years, speckle-tracking echocardiography (STE) has gained prominence as a non-invasive tool providing a more detailed assessment of its mechanical properties. At the same time, advances in omics are providing new insights into the underlying molecular mechanisms of CVD [1,2]. Purpose The aim of the study was to investigate whether proteomic profile is associated with left atrial (LA) strain parameters in the general population without serious CVD, inflammatory diseases and without a history of cancer. Methods The study enrolled 218 participants (mean age 52 ± 10.5 years, 47.2% men) from the Polish population-based Bialystok PLUS study. The exclusion criteria were applied: individuals with a history of inflammatory diseases (psoriasis, rheumatoid arthritis, lupus, inflammatory bowel diseases), with a history of cancer, with a history of serious cardiovascular diseases (after myocardial infarction, coronary artery bypass surgery, coronary artery angioplasty, stroke), individuals with a history of Parkinson's and Alzheimer's disease, individuals taking steroidal or immunosuppressive medication. The ECHO measurements were made using the B-mode ultrasound Vivid 9 (GE Healthcare, Chicago, IL, USA). STE was performed to assess LA phasic function including reservoir (LASr), conduit (LAScd) and contraction (LASct) strain. The apical four-chamber and two-chamber views were analysed to calculate LA strain. Olink® Reveal, a novel, high-throughput platform by Olink Proteomics based on their Proximity Extension Assay (PEA) was to use to identify levels of circulating proteins in small volumes of plasma samples. Nonparametric Spearman’s correlations with the Bonferroni–Hochberg correction for multiple comparisons were used for analysis. Results The mean LASr was 33.0 ± 7.3%, the mean LAScd was -18.0 ± 6.2%, and the mean LASct was -14.9 ± 4.4%. CUB domain-containing protein 1 (CDCP1), Paralemmin-2 (PALM2), Interleukin-6 (IL6) concentrations were negatively associated with the LASr parameter and consequently the function of LA. Cytosolic 5'-nucleotidase 1A (NT5C1A), Leiomodin-1 (LMOD1), CDCP1, Glial fibrillary acidic protein (GFAP), Gamma-interferon-inducible lysosomal thiol reductase (IFI30), IL6, Tumor necrosis factor receptor superfamily member 27 (EDA2R), Heat shock protein beta-6 (HSPB6), C-C motif chemokine 3 (CCL3), Actin filament-associated protein 1-like 1 (AFAP1L1), Testican-1 (SPOCK1) were positively associated with the LAScd parameter and therefore negatively with the LA function (Ryc 1). Conclusions These protein expression patterns suggest their involvement in the regulation of the actin cytoskeleton, fibrosis and inflammation, which adversely affect LA function. A better understanding of the biological function of the above markers may help in the development of new therapeutic approaches and risk stratification for CVD.