Prognostic implications of microvascular complications in patients with diabetes and heart failure with reduced ejection fraction

Patel, Kershaw V.; Pandey, Ambarish

doi:10.1002/ejhf.1253

Cited by 1 publication

(2 citation statements)

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“…Vascular rarefaction is a common feature of heart failure (HF) with preserved or reduced ejection fraction (EF), HFpEF, and HFrEF. 16,17 Endothelial dysfunction could play a dominant role in the pathophysiology and outcomes of HFpEF. 18 In volume-overload hypertrophy, CELF1 expression is mainly increased in cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

“…This situation indicates a CELF1‐mediated coupled event of vascular rarefaction and electric conduction dysregulation. Vascular rarefaction is a common feature of heart failure (HF) with preserved or reduced ejection fraction (EF), HFpEF, and HFrEF 16,17 . Endothelial dysfunction could play a dominant role in the pathophysiology and outcomes of HFpEF 18 .…”

Section: Discussionmentioning

confidence: 99%

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CELF1 promotes vascular endothelial growth factor degradation resulting in impaired microvasculature in heart failure

et al. 2021

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Vascular rarefaction due to impaired angiogenesis is associated with contractile dysfunction and the transition from compensation to decompensation and heart failure. The regulatory mechanism controlling vascular rarefaction during the transition remains elusive. Increased expression of a nuclear RNA-binding protein CUGBP Elavlike family member 1 (CELF1) in the adult heart is associated with the transition from compensated hypertrophy to decompensated heart failure. Elevated CELF1 level resulted in degradation of the major cardiac gap junction protein, connexin 43, in dilated cardiomyopathy (DCM), the most common cause of heart failure. In the present study, we investigated the role of increased CELF1 expression in causing vascular rarefaction in DCM. CELF1 overexpression (CELF1-OE) in cardiomyocytes resulted in reduced capillary density. CELF1-OE mice administered hypoxyprobe showed immunoreactivity and increased mRNA levels of HIF1α, Glut-1, and Pdk-1, which suggested the association of a reduced capillary density-induced hypoxic condition with CELF1 overexpression. Vegfa mRNA level was downregulated in mouse hearts exhibiting DCM, including CELF1-OE and infarcted hearts. Vegfa mRNA level was also downregulated to a similar extent in cardiomyocytes isolated from infarcted hearts by Langendorff preparation, which suggested cardiomyocyte-derived Vegfa expression mediated by CELF1. Cardiomyocyte-specific depletion of CELF1 preserved the capillary density and Vegfa mRNA level in infarcted mouse hearts. Also, CELF1 bound to Vegfa mRNA and regulated Vegfa mRNA stability via the 3′ untranslated region. These results suggest that elevated CELF1 level has dual effects on impairing the functions of cardiomyocytes and microvasculature in DCM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%