Endothelial Dysfunction in Chronic Heart Failure: Assessment, Findings, Significance, and Potential Therapeutic Targets

Alem, Manal M.

doi:10.3390/ijms20133198

Cited by 69 publications

(66 citation statements)

References 113 publications

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“…Endothelial dysfunction is an early event in the development of cardiovascular diseases, such as HF, and is therefore an important indicator of survival [104,105]. It is present in both HFpEF and HFrEF (Table 1) [23,24,106], as shown by a similar loss in cardiac microvascular density [23,24]. However, comorbidities can differentially affect endothelial function, with microvascular complications being more prevalent in HFpEF than in HFrEF [22].…”

Section: Endothelial Dysfunction: a Main Player In Both Hfref And Hfpefmentioning

confidence: 99%

Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding

Simmonds

Cuijpers

Heymans

et al. 2020

Cells

236

219

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Heart failure (HF) is the most rapidly growing cardiovascular health burden worldwide. HF can be classified into three groups based on the percentage of the ejection fraction (EF): heart failure with reduced EF (HFrEF), heart failure with mid-range—also called mildly reduced EF— (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). HFmrEF can progress into either HFrEF or HFpEF, but its phenotype is dominated by coronary artery disease, as in HFrEF. HFrEF and HFpEF present with differences in both the development and progression of the disease secondary to changes at the cellular and molecular level. While recent medical advances have resulted in efficient and specific treatments for HFrEF, these treatments lack efficacy for HFpEF management. These differential response rates, coupled to increasing rates of HF, highlight the significant need to understand the unique pathogenesis of HFrEF and HFpEF. In this review, we summarize the differences in pathological development of HFrEF and HFpEF, focussing on disease-specific aspects of inflammation and endothelial function, cardiomyocyte hypertrophy and death, alterations in the giant spring titin, and fibrosis. We highlight the areas of difference between the two diseases with the aim of guiding research efforts for novel therapeutics in HFrEF and HFpEF.

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Section: Endothelial Dysfunction: a Main Player In Both Hfref And Hfpefmentioning

confidence: 99%

Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding

Simmonds

Cuijpers

Heymans

et al. 2020

Cells

236

219

View full text Add to dashboard Cite

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“…116,117 Endothelial dysfunction in patients with chronic heart failure is associated with increased mortality. 118 Increased adhesion molecule expression, reduced anticoagulant properties, and imbalanced production of vasodilating and vasoconstriction substances all lead to endothelial dysfunction. 119 There are sufficient indications that GDF15 causes endothelial dysfunction by impairing vascular contraction and relaxation, which consequently could have a large impact on the function of the heart, by inducing not only large artery disease but also microvascular disease, which is associated with a deteriorating cardiac function.…”

Section: Effect Of Growth Differentiation Factor 15 On Endothelial Cellsmentioning

confidence: 99%

“…Endothelial dysfunction is crucial mediator of impaired coronary and systemic perfusion and reduced cardiac capacity via directly negatively affecting cardiac remodelling and cardiomyocyte function 116,117 . Endothelial dysfunction in patients with chronic heart failure is associated with increased mortality 118 . Increased adhesion molecule expression, reduced anticoagulant properties, and imbalanced production of vasodilating and vasoconstriction substances all lead to endothelial dysfunction 119 .…”

Section: Growth Differentiation Factor 15 As a Causal Player In Advermentioning

confidence: 99%

Growth differentiation factor 15 in adverse cardiac remodelling: from biomarker to causal player

2020

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Heart failure is a growing health issue as a negative consequence of improved survival upon myocardial infarction, unhealthy lifestyle, and the ageing of our population. The large and complex pathology underlying heart failure makes diagnosis and especially treatment very difficult. There is an urgent demand for discriminative biomarkers to aid disease management of heart failure. Studying cellular pathways and pathophysiological mechanisms contributing to disease initiation and progression is crucial for understanding the disease process and will aid to identification of novel biomarkers and potential therapeutic targets. Growth differentiation factor 15 (GDF15) is a proven valuable biomarker for different pathologies, including cancer, type 2 diabetes, and cardiovascular diseases. Although the prognostic value of GDF15 in heart failure is robust, the biological function of GDF15 in adverse cardiac remodelling is not fully understood. GDF15 is a distant member of the transforming growth factor-β family and involved in various biological processes including inflammation, cell cycle, and apoptosis. However, more research is suggesting a role in fibrosis, hypertrophy, and endothelial dysfunction. As GDF15 is a pleiotropic protein, elucidating the exact role of GDF15 in complex disease processes has proven to be a challenge. In this review, we provide an overview of the role GDF15 plays in various intracellular and extracellular processes underlying heart failure, and we touch upon crucial points that need consideration before GDF15 can be integrated as a biomarker in standard care or when considering GDF15 for therapeutic intervention.

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“…These not only regulate cardiomyocyte contraction but also contribute to interactions in cardiac physiology and pathologies [ 3 , 6 ]. Additionally, due to the unique structure of the coronary vasculature, heart endothelial cell injury leads to severe damage to other heart tissues and organs [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1

et al. 2021

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The CR6-interacting factor1 (CRIF1) mitochondrial protein is indispensable for peptide synthesis and oxidative phosphorylation. Cardiomyocyte-specific deletion of CRIF1 showed impaired mitochondrial function and cardiomyopathy. We developed an endothelial cell-specific CRIF1 deletion mouse to ascertain whether dysfunctional endothelial CRIF1 influences cardiac function and is mediated by the antioxidant protein sirtuin 1 (SIRT1). We also examined the effect of the potent SIRT1 activator SRT1720 on cardiac dysfunction. Mice with endothelial cell-specific CRIF1 deletion showed an increased heart-to-body weight ratio, increased lethality, and markedly reduced fractional shortening of the left ventricle, resulting in severe cardiac dysfunction. Moreover, endothelial cell-specific CRIF1 deletion resulted in mitochondrial dysfunction, reduced ATP levels, inflammation, and excessive oxidative stress in heart tissues, associated with decreased SIRT1 expression. Intraperitoneal injection of SRT1720 ameliorated cardiac dysfunction by activating endothelial nitric oxide synthase, reducing oxidative stress, and inhibiting inflammation. Furthermore, the decreased endothelial junction-associated protein zonula occludens-1 in CRIF1-deleted mice was significantly recovered after SRT1720 treatment. Our results suggest that endothelial CRIF1 plays an important role in maintaining cardiac function, and that SIRT1 induction could be a therapeutic strategy for endothelial dysfunction-induced cardiac dysfunction.

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Endothelial Dysfunction in Chronic Heart Failure: Assessment, Findings, Significance, and Potential Therapeutic Targets

Cited by 69 publications

References 113 publications

Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding

Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding

Growth differentiation factor 15 in adverse cardiac remodelling: from biomarker to causal player

SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1

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