Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients

• Published in: Proteomics. Clinical applications Vol. 15; no. 4
• Main Authors: Xhakollari, Liana, Jujic, Amra, Molvin, John, Nilsson, Peter, Holm, Hannes, Bachus, Erasmus, Leosdottir, Margret, Grubb, Anders, Christensson, Anders, Magnusson, Martin
• Format: Journal Article
• Language: English
• Published: 01.07.2021
• Subjects: atherosclerosis; Cardiac and Cardiovascular Systems; cell proliferation; Clinical Medicine; heart failure; Kardiologi; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Shrunken pore syndrome
• ISSN: 1862-8346; 1862-8354; 1862-8354
• DOI: 10.1002/prca.202000089

Purpose The “Shrunken pore syndrome” (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatinC/eGFRcreatinine‐ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure. Experimental Design Plasma samples from 300 individuals in HARVEST‐Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9 ± 11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni‐corrected p‐value of 0.05/92 = 5.4 × 10−4 was considered significant in the initial age and sex‐adjusted analyses. Presence of SPS was defined as eGFRcystatinC ≤ 60% of eGFRcreatinine. Results SPS presented with significant associations (p < 5.4 × 10−4) in age and sex‐adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin‐2 receptor subunit alpha, and tyrosine‐protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments. Conclusions and clinical relevance In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation.