{"id":387713,"date":"2024-11-10T00:01:00","date_gmt":"2024-11-09T23:01:00","guid":{"rendered":"https:\/\/medizinonline.com\/?p=387713"},"modified":"2024-10-07T15:29:07","modified_gmt":"2024-10-07T13:29:07","slug":"new-perspectives-on-the-role-of-corin","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/new-perspectives-on-the-role-of-corin\/","title":{"rendered":"New perspectives on the role of Corin"},"content":{"rendered":"\n<p><strong>In recent decades, the central role of natriuretic peptides (NPs) in the interaction between the heart and kidneys has been uncovered.\nThese peptides, especially the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP), are crucial regulators of fluid and electrolyte balance.\nAmong other things, they control sodium excretion, blood pressure and the volume of the extracellular fluid space.  <\/strong><\/p>\n\n<!--more-->\n\n<p><em>(red)  <\/em>A key enzyme in the activation of these peptides is corin, a transmembrane serine protease that is expressed not only in the heart but also in the kidneys.\nThis finding provides new insights into the autonomic function of the kidneys in the regulation of sodium and water balance and challenges conventional notions of the cardiorenal axis. <\/p>\n\n<h3 id=\"corin-and-the-activation-of-anp-a-central-role-in-the-heart-and-kidney\" class=\"wp-block-heading\">Corin and the activation of ANP: a central role in the heart and kidney<\/h3>\n\n<p>Atrial natriuretic peptide (ANP) is released in response to volume overload or stretching of the atria of the heart.\nCorin, a proteolytic enzyme, is responsible for the conversion of inactive proANP into its active form.\nSimilarly, BNP, which is mainly released from the ventricles of the heart during pressure or volume overload, is activated by the enzyme furin.\nBoth peptides bind to the NPR-A receptor, which mediates a number of physiological effects through the secondary messenger cGMP (cyclic guanosine monophosphate), including the promotion of sodium excretion (natriuresis) and relaxation of vascular smooth muscle.\nThe previous idea was that NPs were produced primarily in the heart and released into the bloodstream to act on the kidneys and other organs.\nHowever, new findings show that corin and ANP are also produced locally in the kidneys, suggesting an independent NP system in the kidney that may function independently of the classical cardiorenal axis.\nThis opens up new perspectives for the role of the kidney in the regulation of sodium and water balance.      <\/p>\n\n<h3 id=\"the-local-np-system-of-the-kidney-autonomous-regulation-of-salt-and-water-balance\" class=\"wp-block-heading\">The local NP system of the kidney: autonomous regulation of salt and water balance<\/h3>\n\n<p>While the heart is considered the most important site of NP synthesis, recent studies show that the kidneys also have components of the NP system, including corin, ANP and the NPR-A receptor.\nThese proteins are localized in different parts of the renal tubule system, particularly in the proximal tubules, the loop of Henle and the collecting ducts.\nActivation of the NPR-A receptor inhibits sodium reabsorption in these tubules, leading to increased sodium excretion and diuresis.\nOf particular note, corin and ANP are co-localized in the same renal segments, indicating that locally produced ANP plays an important role in the autonomic regulation of renal function.   <\/p>\n\n<p>This local production of ANP in the kidneys appears to play a critical role in the regulation of fluid and electrolyte balance, particularly under conditions associated with increased salt loading or fluid retention.\nIn animal models with corin deficiency (Cor-\/-), a reduced ability to excrete sodium was observed, leading to hypertension and heart failure.\nThese results suggest that corin plays a central role in maintaining blood pressure and fluid balance not only in the heart but also in the kidneys.  <\/p>\n\n<h3 id=\"clinical-relevance-of-corin-and-the-natriuretic-peptides\" class=\"wp-block-heading\">Clinical relevance of corin and the natriuretic peptides<\/h3>\n\n<p>Patients with genetic mutations leading to loss of corin function show both cardiovascular and renal abnormalities.\nA recent clinical study described two siblings with homozygous corin deficiency who suffered from hypertension, cardiomyopathy, atrial fibrillation and left atrial fibrosis.\nThese patients showed reduced excretion of electrolytes and creatinine despite high BNP levels, indicating that BNP cannot fully compensate for the absence of ANP.  <\/p>\n\n<p>This raises an interesting question: What is the role of locally produced ANP in the kidneys compared to natriuretic peptides produced in the heart?\nThe results of this study suggest that the absence of ANP in the kidneys, due to corin deficiency, can cause significant impairment of kidney function, even when BNP is elevated as a replacement mechanism.\nThis supports the hypothesis that the renal NP system has an autonomous function that acts independently of the conventional cardiorenal NP system.  <\/p>\n\n<h3 id=\"animal-models-and-genetic-studies-insights-into-the-functioning-of-the-np-system\" class=\"wp-block-heading\">Animal models and genetic studies: Insights into the functioning of the NP system<\/h3>\n\n<p>Animal studies provide important evidence for the role of corin in the cardiorenal axis.\nIn genetically modified mouse models in which corin was knocked out either in the heart (hcKO) or in the kidneys (kcKO), significant differences were found in the ability to excrete sodium and regulate blood pressure.\nIn particular, on a high-salt diet, the kcKO mice developed salt exacerbation of hypertension and renal dysfunction, suggesting that the function of corin in the kidneys is crucial for the regulation of sodium excretion.\nInterestingly, this dysfunction was not as pronounced in the hcKO mice, further emphasizing the important role of the kidneys in this system.\nThese findings are of clinical importance as they suggest that promoting corin activity in the kidneys could be a potential therapeutic strategy for the treatment of hypertension and renal insufficiency.\nEspecially in patients suffering from salt sensitivity or fluid retention, supporting renal ANP production could help to better regulate sodium and water balance.     <\/p>\n\n<h3 id=\"summary-and-outlook\" class=\"wp-block-heading\">Summary and outlook<\/h3>\n\n<p>While the heart continues to play a central role in the regulation of fluid and electrolyte balance, the kidneys have been shown to have their own autonomous NP system that plays an equally important role.\nThis local NP system could play a crucial role in the regulation of sodium excretion and blood pressure, especially in patients with cardiovascular or renal disease. <\/p>\n\n<p>Given the importance of the NP system for the regulation of fluid and electrolyte balance, new therapeutic strategies to support corin activity in the kidneys could offer promising approaches for the treatment of hypertension, heart failure and renal dysfunction.<\/p>\n\n<p><em>Source: Abassi Z, Hamo-Giladi DB, Kinaneh S, Heyman SN: The endocrine basis of the cardio-renal axis: New perspectives regarding corin.\nPhysiol Rep 2024 Jul; 12(13): e16105.\ndoi: 10.14814\/phy2.16105.\nPMID: 38942727; PMCID: PMC11213627.   <\/em><\/p>\n\n<p><\/p>\n\n<p class=\"has-small-font-size\"><em>CARDIOVASC 2024; 23(3): 36<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>In recent decades, the central role of natriuretic peptides (NPs) in the interaction between the heart and kidneys has been uncovered. These peptides, especially the atrial natriuretic peptide (ANP) and&hellip;<\/p>\n","protected":false},"author":7,"featured_media":387715,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"The endocrine basis of the cardiorenal axis  ","footnotes":""},"category":[11359,11508,11413,11548],"tags":[61466,78852,78853],"powerkit_post_featured":[],"class_list":["post-387713","post","type-post","status-publish","format-standard","has-post-thumbnail","category-cardiology","category-education","category-nephrology","category-rx-en","tag-anp-en","tag-corin-en","tag-sodium-en","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-04-11 08:54:36","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":387707,"slug":"nouvelles-perspectives-sur-le-role-de-corin","post_title":"Nouvelles perspectives sur le r\u00f4le de Corin","href":"https:\/\/medizinonline.com\/fr\/nouvelles-perspectives-sur-le-role-de-corin\/"},"it_IT":{"locale":"it_IT","id":387701,"slug":"nuove-prospettive-sul-ruolo-di-corin","post_title":"Nuove prospettive sul ruolo di Corin","href":"https:\/\/medizinonline.com\/it\/nuove-prospettive-sul-ruolo-di-corin\/"},"pt_PT":{"locale":"pt_PT","id":387694,"slug":"novas-perspectivas-sobre-o-papel-da-corin","post_title":"Novas perspectivas sobre o papel da Corin","href":"https:\/\/medizinonline.com\/pt-pt\/novas-perspectivas-sobre-o-papel-da-corin\/"},"es_ES":{"locale":"es_ES","id":387687,"slug":"nuevas-perspectivas-sobre-el-papel-de-corin","post_title":"Nuevas perspectivas sobre el papel de Corin","href":"https:\/\/medizinonline.com\/es\/nuevas-perspectivas-sobre-el-papel-de-corin\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/387713","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=387713"}],"version-history":[{"count":1,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/387713\/revisions"}],"predecessor-version":[{"id":387716,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/387713\/revisions\/387716"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/387715"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=387713"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=387713"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=387713"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=387713"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}