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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="editorial" dtd-version="1.1" specific-use="sps-1.8" xml:lang="en">
  <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 pub-id-type="publisher-id" specific-use="scielo-v3">JWpFnBJBdsbDmhySKCVvxCk</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2019000200163</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180259</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Exercise and Garlic Modulate microRNAs Involved in Diabetic Cardiopathy</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3119-5723</contrib-id>
          <name>
            <surname>Lima</surname>
            <given-names>Aline Regina Ruiz</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <institution content-type="orgname">Universidade Estadual Paulista</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina de Botucatu</institution>
          <addr-line>
            <city>Botucatu</city>
            <state>SP</state>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Faculdade de Medicina de Botucatu - Universidade Estadual Paulista (UNESP) - Botucatu, SP - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Aline Regina Ruiz Lima,</bold> Rodovia Ant&#244;nio Butignoli, 10 km. Postal Code 18618-970, Rubi&#227;o Junior, Botucatu, SP - Brazil. E-mail: <email>alinerrlima@gmail.com</email>
				</corresp>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>02</month>
        <year>2019</year>
      </pub-date>
      <volume>112</volume>
      <issue>2</issue>
      <fpage>163</fpage>
      <lpage>164</lpage>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <related-article ext-link-type="doi" id="r01" page="154-162" related-article-type="commentary-article" vol="112" xlink:href="10.5935/abc.20190002"/>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Diabetes Mellitus/complications</kwd>
        <kwd>Exercise/prevention &amp; control</kwd>
        <kwd>MicroRNAs</kwd>
        <kwd>Heart Diseases</kwd>
        <kwd>Angiogenesis Inducing Agents</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <p>Diabetes mellitus (DM) is a major risk factor for cardiovascular disorders and stroke development and is associated with increased morbidity and mortality.<xref ref-type="bibr" rid="B1">1</xref> The prevalence of diabetes is increasing at an alarming rate worldwide. Indeed, according to estimates of the International Diabetes Federation, 552 million people are expected to be diabetic in 2030.<xref ref-type="bibr" rid="B2">2</xref> Although a definitive cure is not on the horizon, with proper management, diabetic patients can attenuate the development of serious complications that reduce life quality and expectancy. Facing a considerable rate of occurrence and prognosis complications, studies focusing on high efficiency and low toxicity treatments are of great importance.<xref ref-type="bibr" rid="B3">3</xref>
		</p>
    <p>MicroRNAs are small non-coding RNAs controlling gene expression and participating in many physiopathological processes. These small molecules are getting a lot of attention nowadays since they are universally recognized as major regulators of gene expression and as key controllers of several biological and pathological processes.<xref ref-type="bibr" rid="B4">4</xref> They are essential intracellular mediators in a variety of cellular processes, such as inflammation, mitochondrial metabolism, apoptosis, among others. Therefore, miRNAs could be potential targets to treat some chronic diseases. Besides, these molecules can also be used as early biomarkers, once they are released in urine and blood when in presence of tissue lesion.<xref ref-type="bibr" rid="B5">5</xref> Recently, it was verified that miRNAs are also involved in cardiovascular disorders, especially those which impaired angiogenesis is observed.<xref ref-type="bibr" rid="B6">6</xref>
		</p>
    <p>Considering this scenario, Mostafa et al.<xref ref-type="bibr" rid="B7">7</xref> evaluated the effects of garlic consumption and voluntary exercise, alone and together, on microRNAs 126 and 210, involved in cardiac angiogenesis, in diabetic rats.</p>
    <p>Garlic, <italic>Allium sativum L</italic>, is commonly used in traditional phytotherapy and there are many studies showing its beneficial effects in several disorders, such as cancer, cardiovascular diseases and diabetes. Also, some authors already showed its effects in angiogenesis.<xref ref-type="bibr" rid="B8">8</xref> Indeed, Mostafa et al.,<xref ref-type="bibr" rid="B7">7</xref> found that diabetes reduced cardiac angiogenesis and garlic consumption increased this angiogenesis in diabetic rats.</p>
    <p>Aerobic exercise is a non-pharmacological therapeutic approachable to improve cardiovascular health in general. Regular practice of exercises results in several health benefits, such as improvement in body composition, physical capacity, insulin resistance, endothelial function, arterial hypertension, and quality of life.<xref ref-type="bibr" rid="B9">9</xref> Besides these benefits, exhaustive exercise practice can contribute to oxidative stress, producing reactive oxygen species (ROS). In animal models, some authors believe that voluntary exercises could show more positive effects.<xref ref-type="bibr" rid="B10">10</xref> In fact, Mostafa et al.<xref ref-type="bibr" rid="B7">7</xref> observed that voluntary exercises reduced triglycerides and LDL cholesterol serum levels and enhanced HDL serum levels and HDL/LDL ratio in comparison to the diabetic control group.</p>
    <p>In Mostafa study,<xref ref-type="bibr" rid="B7">7</xref> miRNAs 126 expression is reduced in diabetic rats. Both treatments, physical exercise or garlic ingestion, were able to increase its expression. Interestingly, when taken together, exercise and garlic, there was an additional increase in miRNA 126 expression. MicroRNA 126 is endothelium-specific, modulating angiogenesis and contributing to endothelium homeostasis. Possibly, miRNA 126 acts through inhibition of negative regulators of VEGF pathway.<xref ref-type="bibr" rid="B11">11</xref>
		</p>
    <p>In response to hypoxia conditions, endothelium cells increase miRNA 210 expression to promote angiogenesis. In the same way, other authors have described the high expression of this miRNA in hyperglycemia contexts, such as diabetes.<xref ref-type="bibr" rid="B12">12</xref> These studies corroborate Mostafa et al. results, that showed increased miRNA 210 in diabetic rats. This expression was reduced with both treatments, voluntary exercise or garlic consumption, and there was a bigger reduction when taken together.</p>
    <p>It is well known that physical exercise has positive effects in controlling glycemia levels. Moreover, practice of physical exercise is recommended to good health maintenance and quality of life.<xref ref-type="bibr" rid="B13">13</xref>
		</p>
    <p>A systematic review of garlic effects on lipidic and glucose parameters in diabetic patients was recently published. The authors concluded that garlic can reduce lipid profile as well as glucose parameters and be therapeutically effective in patients with cardiovascular diseases and diabetes.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>
		</p>
    <p>Some of those positive effects obtained by physical exercise and garlic ingestion may be to modulation of specific microRNAs, according to Mostafa and collaborators. It is interesting to observe that the response to those treatments was amplified when they were combined, almost like an adjuvant effect.</p>
    <p>Although these promising and interesting results, more studies on what mechanisms and which intracellular pathways modulate microRNAs expression involved in the cardiac angiogenesis and lipidic profile improvement provided by voluntary physical exercise and garlic consumption in diabetes mellitus are necessary.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other">
        <p>Short Editorial related to the article: The Effect of Garlic and Voluntary Exercise on Cardiac Angiogenesis in Diabetes: The Role of MiR-126 and MiR-210</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Exerc&#237;cio e Modula&#231;&#227;o de MicroRNA do Alho Envolvidos na Cardiopatia Diab&#233;tica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3119-5723</contrib-id>
          <name>
            <surname>Lima</surname>
            <given-names>Aline Regina Ruiz</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <institution content-type="original">Faculdade de Medicina de Botucatu - Universidade Estadual Paulista (UNESP) - Botucatu, SP - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Aline Regina Ruiz Lima,</bold> Rodovia Ant&#244;nio Butignoli, 10 km. CEP 18618-970, Rubi&#227;o Junior, Botucatu, SP - Brasil. E-mail: <email>alinerrlima@gmail.com</email>
				</corresp>
      </author-notes>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Diabetes Mellitus/complica&#231;&#245;es</kwd>
        <kwd>Exerc&#237;cio/preven&#231;&#227;o e controle</kwd>
        <kwd>MicroRNAs</kwd>
        <kwd>Cardiopatias</kwd>
        <kwd>Indutores da Angiog&#234;nese</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>O diabetes melito (DM) &#233; um importante fator de risco para dist&#250;rbios cardiovasculares e desenvolvimento de AVC e est&#225; associado ao aumento da morbidade e mortalidade.<xref ref-type="bibr" rid="B1">1</xref> A preval&#234;ncia de diabetes est&#225; aumentando em um ritmo alarmante em todo o mundo. Na verdade, de acordo com estimativas da International Diabetes Federation, espera-se que 552 milh&#245;es de pessoas sejam diab&#233;ticas em 2030.<xref ref-type="bibr" rid="B2">2</xref> Embora uma cura definitiva, com um manejo adequado, n&#227;o esteja prevista, os pacientes diab&#233;ticos podem atenuar o desenvolvimento de complica&#231;&#245;es s&#233;rias que reduzem a qualidade e a expectativa de vida. Diante de uma taxa consider&#225;vel de complica&#231;&#245;es de ocorr&#234;ncia e progn&#243;stico, estudos com foco em tratamentos de alta efici&#234;ncia e baixa toxicidade s&#227;o de grande import&#226;ncia.<xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>Os microRNA s&#227;o pequenos RNA n&#227;o codificantes que controlam a express&#227;o g&#234;nica e participam de muitos processos fisiopatol&#243;gicos. Atualmente, essas pequenas mol&#233;culas est&#227;o recebendo muita aten&#231;&#227;o, pois s&#227;o universalmente reconhecidas como reguladores importantes da express&#227;o g&#234;nica e como principais controladores de v&#225;rios processos biol&#243;gicos e patol&#243;gicos.<xref ref-type="bibr" rid="B4">4</xref> S&#227;o mediadores intracelulares essenciais em v&#225;rios processos celulares, como inflama&#231;&#227;o, metabolismo mitocondrial, apoptose, entre outros. Portanto, os miRNA podem ser alvos potenciais para o tratamento de algumas doen&#231;as cr&#244;nicas. Al&#233;m disso, essas mol&#233;culas tamb&#233;m podem ser utilizadas como biomarcadores precoces, uma vez que s&#227;o liberadas na urina e no sangue quando em presen&#231;a de les&#227;o tecidual.<xref ref-type="bibr" rid="B5">5</xref> Recentemente, verificou-se que os miRNA tamb&#233;m est&#227;o envolvidos em dist&#250;rbios cardiovasculares, sendo que especialmente aqueles que prejudicaram a angiog&#234;nese foram observados.<xref ref-type="bibr" rid="B6">6</xref>
			</p>
      <p>Considerando esse cen&#225;rio, Mostafa et al.,<xref ref-type="bibr" rid="B7">7</xref> avaliaram os efeitos do consumo de alho e do exerc&#237;cio volunt&#225;rio, isoladamente e em conjunto, nos microRNA 126 e 210, envolvidos na angiog&#234;nese card&#237;aca, em ratos diab&#233;ticos.</p>
      <p>O alho, <italic>Allium sativum L</italic>, &#233; comumente usado em fitoterapia tradicional e h&#225; muitos estudos mostrando seus efeitos ben&#233;ficos em v&#225;rios dist&#250;rbios, como c&#226;ncer, doen&#231;as cardiovasculares e diabetes. Al&#233;m disso, alguns autores j&#225; mostraram seus efeitos na angiog&#234;nese.<xref ref-type="bibr" rid="B8">8</xref> De fato, Mostafa et al.,<xref ref-type="bibr" rid="B7">7</xref> constataram que o diabetes reduziu a angiog&#234;nese card&#237;aca e o consumo de alho aumentou essa angiog&#234;nese em ratos diab&#233;ticos.</p>
      <p>O exerc&#237;cio aer&#243;bico &#233; um tratamento n&#227;o farmacol&#243;gico acess&#237;vel para melhorar a sa&#250;de cardiovascular em geral. A pr&#225;tica regular de exerc&#237;cios resulta em v&#225;rios benef&#237;cios para a sa&#250;de, como melhora da composi&#231;&#227;o corporal, capacidade f&#237;sica, resist&#234;ncia &#224; insulina, fun&#231;&#227;o endotelial, hipertens&#227;o arterial e qualidade de vida.<xref ref-type="bibr" rid="B9">9</xref> Al&#233;m desses benef&#237;cios, a pr&#225;tica exaustiva de exerc&#237;cios pode contribuir para o estresse oxidativo, produzindo esp&#233;cies reativas de oxig&#234;nio (ROS). Em modelos animais, alguns autores acreditam que os exerc&#237;cios volunt&#225;rios poderiam apresentar efeitos mais positivos.<xref ref-type="bibr" rid="B10">10</xref> Na verdade, Mostafa et al.,<xref ref-type="bibr" rid="B7">7</xref> observaram que os exerc&#237;cios volunt&#225;rios reduziram os n&#237;veis s&#233;ricos de triglicer&#237;deos e colesterol LDL e aumentaram os n&#237;veis s&#233;ricos de HDL e a raz&#227;o HDL/LDL em compara&#231;&#227;o com o grupo controle diab&#233;tico.</p>
      <p>No estudo de Mostafa et al.,<xref ref-type="bibr" rid="B7">7</xref> a express&#227;o de miRNA 126 &#233; reduzida em ratos diab&#233;ticos. Ambos os tratamentos, exerc&#237;cio f&#237;sico ou ingest&#227;o de alho, foram capazes de aumentar sua express&#227;o. Curiosamente, quando tomados em conjunto, exerc&#237;cio e alho, houve um aumento adicional na express&#227;o de miRNA 126. O microRNA 126 &#233; espec&#237;fico do endot&#233;lio, modulando a angiog&#234;nese e contribuindo para a homeostase do endot&#233;lio. Possivelmente, o miRNA 126 atua atrav&#233;s da inibi&#231;&#227;o dos reguladores negativos da via do VEGF.<xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>Em resposta &#224;s condi&#231;&#245;es de hip&#243;xia, as c&#233;lulas do endot&#233;lio aumentam a express&#227;o do miRNA 210 para promover a angiog&#234;nese. Da mesma maneira, outros autores descreveram a alta express&#227;o desse miRNA em contextos de hiperglicemia, como o diabetes.<xref ref-type="bibr" rid="B12">12</xref> Esses estudos corroboram os resultados de Mostafa et al., que apresentaram aumento de miRNA 210 em ratos diab&#233;ticos. Esta express&#227;o foi reduzida com ambos os tratamentos, exerc&#237;cio volunt&#225;rio ou consumo de alho, e houve uma redu&#231;&#227;o maior quando tomadas em conjunto.</p>
      <p>Sabe-se bem que o exerc&#237;cio f&#237;sico tem efeitos positivos no controle dos n&#237;veis de glicemia. Al&#233;m disso, recomenda-se a pr&#225;tica de exerc&#237;cios f&#237;sicos para uma boa manuten&#231;&#227;o da sa&#250;de e qualidade de vida.<xref ref-type="bibr" rid="B13">13</xref>
			</p>
      <p>Uma revis&#227;o sistem&#225;tica dos efeitos do alho sobre os par&#226;metros lip&#237;dicos e glic&#234;micos em pacientes diab&#233;ticos foi recentemente publicada. Os autores conclu&#237;ram que o alho pode reduzir o perfil lip&#237;dico e os par&#226;metros glic&#234;micos e ser terapeuticamente efetivo em pacientes com doen&#231;as cardiovasculares e diabetes.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>
			</p>
      <p>Alguns desses efeitos positivos obtidos pelo exerc&#237;cio f&#237;sico e ingest&#227;o de alho podem ser modulados por microRNA espec&#237;ficos, de acordo com Mostafa e colaboradores. &#201; interessante observar que a resposta a esses tratamentos foi amplificada quando combinados, quase como um efeito adjuvante.</p>
      <p>Apesar destes resultados promissores e interessantes, s&#227;o necess&#225;rios mais estudos sobre quais mecanismos e quais vias intracelulares modulam a express&#227;o de microRNA envolvidos na angiog&#234;nese card&#237;aca e melhora do perfil lip&#237;dico proporcionado pelo exerc&#237;cio f&#237;sico volunt&#225;rio e consumo de alho no diabetes melito.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>Minieditorial referente ao artigo: O Efeito do Alho e Exerc&#237;cio Volunt&#225;rio na Angiog&#234;nese Card&#237;aca no Diabetes: O papel do MiR-126 e do MiR-210</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
