Seeking Candidate Molecules as Prognostic Healing Markers in Chronic Venous Ulcers

Abstract

Faculdade de Medicina de Botucatu, FMB) for making available all the resources and equipment that contributed to this work. We acknowledge the Mass Spectrometry Laboratory at the Brazilian Biosciences National Laboratory, CNPEM, Campinas, SP, Brazil, for its support with the mass spectrometric analysis. 3 ABSTRACT 1 Seeking and identifying biomarker molecules in inflammatory exudate of chronic 2 venous ulcers (CVUs) can aid health professionals in the healing prognosis. The 3 therapeutic failure or cure is related to the quantitative expression of determinate 4proteins. This work aimed to identify the proteins expressed in inflammatory exu-5 dates from CVUs and correlate them with reduction or increase in the wound size. 6 For 90 days, 28 participants that received standard treatment for 37 CVUs were 7 monitored. The inflammatory exudates were collected before treatment initiation 8 (T=0) and analyzed via the Label-free Shotgun. After 90 days the wound area was 9 reduced in 25 (67.6%) of them. Mass spectrometry analysis of all the inflammatory 10 exudates showed four proteins differentially expressed and related to favorable or 11 unfavorable evolution of the healing process. Complement C3 and ceruloplasmin 12 were identified in all the lesions analyzed and were expressed differentially in le-13 sions that presented diminished area in the studied period. Apoliprotein A1 and 14 neutrophil defensin-1 presented differential expression in ulcers that either did not 15 diminish or augmented their wound area through 90 days. These results suggest 16 that Complement C3, Ceruloplasmin, Apoliprotein A1 and Neutrophil-defensin-1 17 proteins are potential candidate molecules for prognostic healing markers in chron-18 ic venous ulcers. 19Keywords: Chronic venous ulcers, non-healing ulcers, inflammatory exudate, 20 mass spectrometry, prognostic biomarkers. 21 22the Western world [1]. Epidemiological studies performed in the last decade evi-26 denced the frightening perspective of an estimated prevalence between 34.5 and 27 150.8 million persons affected [2,[3][4][5][6]. Chronic leg ulcers are lesions that generally 28 last longer than 6 weeks and in some cases more than 20 years, frequently recur 29 and are related to complications from venous insufficiency in the lower limbs [7,8]. 30The treatment is prolonged, onerous to the health systems, and has im-31 portant social impact since it contributes to absences from work [9][10][11][12]. The pa-32 tients evolve with restricted mobility, social isolation and a worsening quality of life 33 [13,14]. These aspects affect mental health by increasing sleep disturbances [15], 34 evolving with anxiety and subsequent depression [16]. Given that some cases heal 35 and others do not, science has been searching for years for possible prognostic 36 mechanisms of healing. 37In this context, the investigative approach of proteomic analysis of human 38 bodily fluids has been viewed as powerful analytic tool for discovering molecular 39 markers that can aid in the diagnosis and progno...

Chronic venous ulcers: a review on treatment with fibrin sealant and prognostic advances using proteomic strategies

“…This prognosis is only possible by evaluating the expression of the proteins isolated in the exudates by means of shotgun label-free strategy. Those easily healed express mainly complement C3 and ceruloplasmin, whereas those that are difficult to heal express apoliproteína a1 and neutrophil defensina-1 [69].…”

“…In another work, Cavassan et al [69] identified differentially expressed proteins in the inflammatory exudate of VUs and correlated them with the ease or difficulty of healing. The same 37 ulcers indicated in the 2019 study [68] were monitored for 90 days.…”