CHA2DS2-VASc score and blood biomarkers to identify patients with atrial high rate episodes and paroxysmal atrial fibrillation: the role of TIMP-4 regulation —Authors’ reply

In our patient cohort, we have investigated a biomarker pattern with discriminatory potential for the prevalence of atrial arrhythmias. We chose tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) among others as candidate markers for evaluation based on their previously reported involvement in atrial extracellular matrix remodelling as a substrate for atrial fibrillation.1 The commenting authors raise an important issue by citing clinical studies that have found TIMP-4 to be downregulated in atrial fibrillation (AF),2 whereas we and also others reported increased levels of TIMP-4.1,3 Obviously, current understanding of the dynamics of extracellular matrix (ECM) composition during atrial remodelling is incomplete, and the role of single components of MMPs and TIMPs, in particular TIMP-4, needs further clarification. We acknowledge the cited evidence in the commenting letter linking TIMP-4 to upstream miR-146b-5p, although in our opinion this does not aid in explaining differences in biomarker abundance in the clinical studies discussed. Several potential explanations may be considered: (i) TIMP-4 is abundant in cardiovascular structures, but also highly expressed in brain, ovary, and skeletal muscle. We cannot exclude that non-cardiovascular (not assessed) co-morbidities may have contributed to elevated TIMP-4 in serum in our cohort. Notably the difference in TIMP-4 reflected a majority of patients with Atrial High-Rate Episodes and AF (AHRE/A...
Source: Europace - Category: Cardiology Source Type: research