Roles of Biomarkers in Myocardial Fibrosis

Ding Yuejia, Wang Yuan, Zhang Wanqin, Jia Qiujin, Wang Xiaoling, Li Yanyang, Lv Shichao, Zhang Junping

Table 1 Biomarkers of myocardial fibrosis (collagen synthesis, breakdown, metabolism).

Biomarkers Studied Condition Test Location Main findings Reference PICP HCM patients Plasma PICP ↑ [10] Hypertension patients Serum PICP ↑ [11] HF rats Plasma PICP ↓ [12] HF patients Serum PICP ↑ [13] PINP HFrEF patients Serum PINP ↑ [18] MI rats Plasma PINP ↑ [19] HCM patients Serum Not predictive in fibrosis [20] PIIINP DCM patients Serum PIIINP ↑ [25] HFrEF patients Serum PIIINP ↑, positively associated with diastolic function [26] CoA patients Serum PIIINP ↑, positively associated with LVMI and RWT [27] Hypertension patients Serum PIIINP ↑, inversely associated with diastolic functions [28] MI rats Serum PIIINP ↑ [29] CITP HF patients Serum CITP ↑ [20] HF and AF patients Serum CITP ↑ [32-33] DCM patients Serum Not predictive in fibrosis [34] AMI patients Serum CITP ↑, predicts cardiovascular mortality [35] MMPs HCM patients Serum MMP-2 ↓, MMP-9 was positively associated with fibrosis [44] systolic HF patients Serum MMP-1↑ [45-46] DM rats Myocardial tissues MMP2↓, MMP7, MMP11, MMP13, MMP16↑ [47] TIMPs 2K1C hypertension rats Myocardial tissues TIMP-4↑ [58] TTC patients Serum TIMP-1 and MMP-2 ↑ [59] HF patients Serum TIMP-1↑ [60] TGF-β MI mice Myocardial tissues anti-TGF-β treated: collagen production ↓, matrix-metalloproteinase ↑ [66] Pressure-overload rats Myocardial tissues anti-TGF-β treated: fibroblast activation ↓, collagen mRNA induction ↓ [67] TAC mice Myocardial tissues anti-TGF-βtreated: perivascular and interstitial fibrosis ↓ [68] Smads TAC mice Cardiac tissues Smad3 or Smad2/3 deletion: cardiac fibrosis↓ [72] Smad3-deficient mice Myocardial tissues Collagen content and deposition ↓ [73] CTGF DCM rats Myocardial tissues CTGF/CCN2 gene silencing: cardiac function ↑, myocardial fibrosis and left ventricular hypertrophy ↓ [81] MI rats Myocardial tissues CTGF ↑ [83] Chronic HF patients Plasma CTGF ↑ [84] Corin HF patients Plasma Corin ↓ [85] HF canines Myocardial tissues Corin ↓ [89] HCM disease Cardiomyocytes Corin↑ [90] EndoMT ISO-induced fibrosis Myocardial tissues α-SMA and vimentin: ↑ with a peak on day 3, and then gradually↓ [92] DCM rats Myocardial tissues a-SMA, fibronectin and vimentin↑ [93] In vitro Mouse embryonic fibroblasts Vimentin deletion: WF-A did not change half-lives of collagen mRNAs [94] Gal-3 Myocardial I/R injury rats Myocardial tissues Gal-3 ↑ [102] AMI patients Serum Gal-3 ↑ after AMI and then ↓ within 5 days [103] Acute HF patients Serum Gal-3 ↑ [104] CAD patients Plasma Gal-3 is positively correlated with cardiovascular deaths [105] TNF-α and interleukin Cardiomyocyte fibrosis Cardiomyocytes TNF-α, IL-6 IL-1β levels and collagen I and III mRNA expressions ↑ [108] HCM patients Plasma IL-4, IL-6, and IL-10 ↑ [97] IL-11 knockout mice Myocardial tissues Fibrosis↓ after either transverse aortic constriction or AngII infusion [109] Other Molecules HFrEF patients Serum RLN1↑ [115] ISO-induced cardiac fibrosis Myocardial tissues GSHR deletion: myocardial fibrosis ↑ [116] VHD mice Myocardial tissues ADAMTS-1↑ [117]