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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">MkRjbNZRGwDzgFNnfDbwJPP</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2024001200202</article-id>
      <article-id pub-id-type="other">00202</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20240735</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Desafios e Perspectivas dos Biomarcadores de Fibrose Card&#237;aca: Do Diagn&#243;stico &#224; Aplica&#231;&#227;o Cl&#237;nica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0003-1159-5030</contrib-id>
          <name>
            <surname>Santos</surname>
            <given-names>Priscila Portugal dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Damatto</surname>
            <given-names>Ricardo Luiz</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Estadual Paulista J&#250;lio de Mesquita Filho Campus de Botucatu</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina de Botucatu</institution>
          <addr-line>
            <named-content content-type="city">Botucatu</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Estadual Paulista J&#250;lio de Mesquita Filho Campus de Botucatu &#8211; Faculdade de Medicina de Botucatu, Botucatu, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Faculdade de Ci&#234;ncias Sociais e Agr&#225;rias de Itapeva</institution>
          <addr-line>
            <named-content content-type="city">Itapeva</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Faculdade de Ci&#234;ncias Sociais e Agr&#225;rias de Itapeva, Itapeva, SP &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><label>Correspond&#234;ncia:</label><bold>Priscila Portugal dos Santos</bold> &#8226; Faculdade de Medicina de Botucatu &#8211; UNESP &#8211; Cl&#237;nica M&#233;dica &#8211; Distrito de Rubi&#227;o Junior, s/n. CEP <postal-code>18618-970</postal-code>, Botucatu, SP &#8211; Brasil E-mail: <email>pripolmed@yahoo.com.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>10</day>
        <month>02</month>
        <year>2025</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <year>2024</year>
      </pub-date>
      <volume>121</volume>
      <issue>12</issue>
      <elocation-id>e20240735</elocation-id>
      <history>
        <date date-type="received">
          <day>04</day>
          <month>11</month>
          <year>2024</year>
        </date>
        <date date-type="rev-recd">
          <day>06</day>
          <month>11</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>09</day>
          <month>11</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>Este &#233; um artigo de acesso aberto distribu&#237;do sob os termos da licen&#231;a de atribui&#231;&#227;o pelo Creative Commons</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Fibrose Endomioc&#225;rdica</kwd>
        <kwd>Col&#225;geno</kwd>
        <kwd>Matriz Extracelular</kwd>
        <kwd>Biomarcadores</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="11"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>Conforme relatado por Cheng-Mei et al.,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> a fibrose mioc&#225;rdica est&#225; presente em diversas doen&#231;as card&#237;acas e pode ter impacto negativo no cora&#231;&#227;o. Ela desempenha papel central na disfun&#231;&#227;o e fal&#234;ncia card&#237;aca em v&#225;rias patologias, al&#233;m de ser forte indicador de desfechos cl&#237;nicos desfavor&#225;veis e de mortalidade.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> No entanto, &#233; essencial reconhecer que a fibrose &#233; um processo complexo e heterog&#234;neo, que em algumas condi&#231;&#245;es card&#237;acas pode ter papel importante, como ap&#243;s infarto do mioc&#225;rdio. Nessa situa&#231;&#227;o, a fibrose atua como um mecanismo reparador, substituindo cardiomi&#243;citos mortos por tecido cicatricial. Essa resposta fibr&#243;tica inicial &#233; fundamental para evitar a ruptura card&#237;aca, complica&#231;&#227;o grave e fatal, que &#233; uma das principais causas de morte em pacientes com infarto agudo do mioc&#225;rdio.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>A fibrose card&#237;aca caracteriza-se pelo ac&#250;mulo excessivo de componentes da matriz extracelular (MEC), especialmente col&#225;genos, no mioc&#225;rdio.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> &#201; importante compreender que esse processo envolve mais do que apenas a quantidade de col&#225;geno; a caracteriza&#231;&#227;o da fibrose inclui tamb&#233;m a qualidade do col&#225;geno, a propor&#231;&#227;o entre os diferentes tipos de fibras e o grau de <italic>cross-linking</italic> do col&#225;geno.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> O col&#225;geno tipo I, predominante na MEC card&#237;aca e vascular, contribui para a resist&#234;ncia e rigidez do tecido devido &#224; sua estrutura espessa e densa. J&#225; o col&#225;geno tipo III, por ser mais flex&#237;vel, promove a complac&#234;ncia da MEC. A elasticidade do mioc&#225;rdio &#233;, determinada pela propor&#231;&#227;o entre as fibras de col&#225;geno tipo I e tipo III.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> Al&#233;m disso, o grau de liga&#231;&#245;es covalentes entre as microfibrilas, ou seja, o <italic>cross-linking</italic>, &#233; fator cr&#237;tico na rigidez das fibras de col&#225;geno, tornando-as mais resistentes &#224; degrada&#231;&#227;o e contribuindo para o enrijecimento do tecido.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Portanto, para melhor compreens&#227;o do processo de fibrose card&#237;aca, e desenvolvimento de novas terapias e m&#233;todos diagn&#243;sticos, &#233; fundamental avaliar a quantidade, a qualidade e o grau de <italic>cross-linking</italic> do col&#225;geno.</p>
    <p>Embora a fibrose mioc&#225;rdica seja um elemento comum entre diversas doen&#231;as card&#237;acas, os m&#233;todos atuais para sua detec&#231;&#227;o e diagn&#243;stico cl&#237;nico ainda s&#227;o limitados e carecem de melhorias quanto &#224; sensibilidade e especificidade.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Para avalia&#231;&#227;o cl&#237;nica, a bi&#243;psia endomioc&#225;rdica (BEM) &#233; considerada o padr&#227;o-ouro, permitindo uma an&#225;lise direta e espec&#237;fica da deposi&#231;&#227;o de col&#225;geno por meio de t&#233;cnicas histol&#243;gicas, como colora&#231;&#227;o com picrosirius red ou tricr&#244;mico de Masson em amostras de bi&#243;psia. Apesar de o procedimento ter baixo risco de complica&#231;&#245;es graves, &#233; invasivo e envolve desafios para a triagem de fibrose em grandes popula&#231;&#245;es, al&#233;m de limita&#231;&#245;es de representatividade, devido ao pequeno volume de tecido examinado e poss&#237;veis erros de amostragem.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup></p>
    <p>Par&#226;metros obtidos por t&#233;cnicas de imagem apresentam certas vantagens em rela&#231;&#227;o &#224; BEM, sendo m&#233;todos n&#227;o invasivos, capazes de avaliar o cora&#231;&#227;o inteiro e adequados para monitoramento da progress&#227;o da doen&#231;a e da resposta ao tratamento. Entretanto, os biomarcadores de imagem apresentam resolu&#231;&#227;o relativamente baixa e uma capacidade limitada de discriminar caracter&#237;sticas espec&#237;ficas do tecido.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup></p>
    <p>Nesse cen&#225;rio, a an&#225;lise de biomarcadores circulantes tem se destacado como estrat&#233;gia promissora, que apresenta boa reprodutibilidade, pode ser implementado para grandes popula&#231;&#245;es mais facilmente, e &#233; independente do operador. Isso a torna &#250;til para triagem populacional, acompanhamento da progress&#227;o da doen&#231;a e efic&#225;cia terap&#234;utica ao longo do tempo. Apesar de muitos biomarcadores terem sido propostos nos &#250;ltimos anos, poucos apresentam resultados consistentes e valida&#231;&#227;o robusta que sustentem sua implementa&#231;&#227;o em ensaios cl&#237;nicos e na pr&#225;tica cl&#237;nica. &#201; prov&#225;vel que a complexidade e heterogeneidade da fibrose mioc&#225;rdica exijam o uso de pain&#233;is de m&#250;ltiplos biomarcadores para melhorar a precis&#227;o diagn&#243;stica.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Nesse contexto, abordagens de bioinform&#225;tica, como a utilizada no estudo,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> desempenham um papel essencial na triagem inicial e identifica&#231;&#227;o de potenciais biomarcadores de fibrose card&#237;aca, enquanto t&#233;cnicas de prote&#244;mica e peptid&#244;mica s&#227;o fundamentais para validar esses candidatos e investigar sua aplicabilidade cl&#237;nica.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p>
    <p>Outro aspecto relevante &#233; analisar se a capacidade diagn&#243;stica e preditiva desses biomarcadores, bem como a avalia&#231;&#227;o de custo-efetividade, em compara&#231;&#227;o com os biomarcadores convencionais,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> &#233; melhor. Ap&#243;s essa etapa, &#233; essencial propor novas tecnologias em sa&#250;de para que os avan&#231;os sejam efetivamente transferidos para a pr&#225;tica cl&#237;nica em benef&#237;cio dos pacientes.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Biomarcadores Potenciais na Fibrose Mioc&#225;rdica: Uma An&#225;lise Bioinform&#225;tica</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S1" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20240735i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Challenges and Perspectives of Cardiac Fibrosis Biomarkers: From Diagnosis to Clinical Application</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0003-1159-5030</contrib-id>
          <name>
            <surname>Santos</surname>
            <given-names>Priscila Portugal dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Damatto</surname>
            <given-names>Ricardo Luiz</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff4">
            <sup>2</sup>
          </xref>
        </contrib>
        <aff id="aff3">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Botucatu</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Estadual Paulista J&#250;lio de Mesquita Filho Campus de Botucatu &#8211; Faculdade de Medicina de Botucatu, Botucatu, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff4">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Itapeva</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Faculdade de Ci&#234;ncias Sociais e Agr&#225;rias de Itapeva, Itapeva, SP &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><label>Mailing Address:</label><bold>Priscila Portugal dos Santos</bold> &#8226; Faculdade de Medicina de Botucatu &#8211; UNESP &#8211; Cl&#237;nica M&#233;dica &#8211; Distrito de Rubi&#227;o Junior, s/n. Postal Code <postal-code>18618-970</postal-code>, Botucatu, SP &#8211; Brazil E-mail: <email>pripolmed@yahoo.com.br</email> </corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Endomyocardial Fibrosis</kwd>
        <kwd>Collagen</kwd>
        <kwd>Extracellular Matrix</kwd>
        <kwd>Biomarkers</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>As reported by Cheng-Mei et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> myocardial fibrosis is present in various cardiac diseases and can negatively impact the heart. It plays a central role in cardiac dysfunction and failure across different pathologies, serving as a strong predictor of poor clinical outcomes and mortality.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> However, it is essential to recognize that fibrosis is a complex and heterogeneous process, which can sometimes play a beneficial role, such as after a myocardial infarction. In this context, fibrosis acts as a reparative mechanism, replacing dead cardiomyocytes with scar tissue. This initial fibrotic response is crucial to prevent cardiac rupture, a severe and often fatal complication and one of the leading causes of death in patients with acute myocardial infarction.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>Cardiac fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) components, especially collagens, within the myocardium.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Understanding this process involves more than just collagen quantity; the characterization of fibrosis also considers collagen quality, the ratio of different fiber types, and the degree of collagen cross-linking.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Type I collagen, which predominates in cardiac and vascular ECM, contributes to tissue strength and stiffness due to its thick, dense structure. Type III collagen, being more flexible, aids in ECM compliance. Thus, myocardial elasticity is determined by the ratio of type I to type III collagen fibers.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> Moreover, the degree of covalent cross-linking among the constituent microfibrils is critical to collagen fiber rigidity, increasing their resistance to degradation and significantly contributing to tissue stiffening.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Therefore, a comprehensive understanding of cardiac fibrosis, aimed at developing new therapies and diagnostic methods, requires evaluating collagen quantity, quality, and cross-linking levels.</p>
      <p>Although myocardial fibrosis is a common feature in various cardiac diseases, current methods for its clinical detection and diagnosis remain limited, with room for improvement in sensitivity and tissue specificity.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> For clinical evaluation, endomyocardial biopsy (EMB) is considered the gold standard, providing a direct, specific analysis of collagen deposition via histological techniques such as picrosirius red or Masson's trichrome staining on biopsy samples. Although EMB is associated with a low risk of serious complications, it is invasive and presents logistical challenges for fibrosis screening in large populations, with limitations in sample representativeness due to the small tissue volume analyzed and potential sampling erros.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup></p>
      <p>Parameters derived from imaging techniques offer certain advantages over EMB, being non-invasive, capable of assessing the entire heart, and suitable for monitoring disease progression and therapeutic response. However, imaging biomarkers have relatively low resolution and limited capacity for discriminating specific tissue characteristics.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>In this scenario, circulating biomarker analysis has emerged as a promising strategy, providing a reproducible, operator-independent, and scalable alternative for large populations. This approach is useful for population-wide screening, monitoring disease progression, and assessing therapeutic efficacy over time. Although numerous biomarkers have been proposed in recent years, few have accumulated consistent data and robust validation to support their implementation in clinical trials and routine clinical practice. Given the complexity and heterogeneity of myocardial fibrosis, it is likely that multiple biomarker panels will be needed to enhance diagnostic accuracy.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> In this context, bioinformatics approaches, such as those applied in the study,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> are crucial for the initial screening and identification of potential cardiac fibrosis biomarkers. At the same time, proteomics and peptidomics techniques are essential for validating these candidates and investigating their clinical applicability.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p>
      <p>Another important consideration is to assess whether the diagnostic and predictive capabilities of these biomarkers, as well as their cost-effectiveness in comparison with conventional biomarkers,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> are superior. Following this evaluation, it is crucial to propose new health technologies to ensure that advancements are effectively transferred to clinical practice for the benefit of patients.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short Editorial related to the article: Potential Biomarkers in Myocardial Fibrosis: A Bioinformatic Analysis</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
