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Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date
Traian Chiuariu1,2, Delia Șalaru1,2, Carina Ureche1,2
1Department of Internal Medicine, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 University Street, 700115 Iasi, Romania.
Insights
Cardiovascular disease and chronic kidney disease often coexist, driven by organ fibrosis in cardio-renal syndrome. This review explores molecular mechanisms and therapeutic targets for cardiac and renal fibrosis.
Area of Science:
- Nephrology
- Cardiology
- Fibrosis Research
Background:
- Cardiovascular disease (CVD) and chronic kidney disease (CKD) frequently coexist, significantly impacting patient outcomes.
- Organ fibrosis is a key factor in cardio-renal syndrome (CRS) pathogenesis, leading to high rates of heart failure and sudden cardiac death.
- Mechanisms include hemodynamic changes, renin-angiotensin-aldosterone system (RAAS) activation, FGF23, Klotho protein, and collagen deposition.
Purpose of the Study:
- To review the molecular mechanisms underlying cardiac and renal fibrosis in patients with CKD and heart failure (HF).
- To highlight emerging therapeutic targets and alternative strategies for managing cardio-renal fibrosis.
Main Methods:
- Literature review focusing on molecular mechanisms of fibrosis in CKD and HF.
- Analysis of proposed mediators and pathways contributing to fibroblast and collagen turnover.
- Identification of novel therapeutic targets and agents.
Main Results:
- Fibrosis significantly contributes to the progression of cardio-renal syndrome.
- Multiple molecular pathways, including RAAS, FGF23, and Klotho, are implicated in cardiac and renal fibrosis.
- Several novel therapeutic strategies are under investigation.
Conclusions:
- Understanding the molecular basis of fibrosis is crucial for managing patients with coexisting CVD and CKD.
- Targeting specific fibrotic pathways offers promising therapeutic avenues for cardio-renal conditions.
- Further research into novel agents like RAAS inhibitors, serelaxin, and IL-11 antibodies is warranted.
Abstract:
Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin-angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition. A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.
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