Endothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse Model

  title={Endothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse Model},
  author={Andreas B Gevaert and Hadis Shakeri and Arthur J.A. Leloup and Cor E. Van Hove and Guido R. Y. De Meyer and Christiaan J M Vrints and Katrien Lemmens and Emeline M. Van Craenenbroeck},
  journal={Circulation: Heart Failure},
Background— Because of global aging, the prevalence of heart failure with preserved ejection fraction (HFpEF) continues to rise. Although HFpEF pathophysiology remains incompletely understood, endothelial inflammation is stated to play a central role. Cellular senescence is a process of cellular growth arrest linked with aging and inflammation. We used mice with accelerated aging to investigate the role of cellular senescence in HFpEF development. Methods and Results— Senescence-accelerated… 

Figures and Tables from this paper

A potential role of autophagy-mediated vascular senescence in the pathophysiology of HFpEF

The mechanisms involved in autophagy-mediated vascular senescence and whether this could be a driver in the development and progression of HFpEF are discussed.

Pharmacological clearance of senescent cells reverses HFpEF hallmarks by decreasing inflammation, endothelial dysfunction and cardiac fibrosis

Aging and chronic inflammation are associated with the development of heart failure with preserved ejection fraction (HFpEF). However, cellular senescence as a potential mechanistic link between

The Endothelial Dysfunction Could Be a Cause of Heart Failure with Preserved Ejection Fraction Development in a Rat Model

Investigation of endothelial and cardiac function in 15, 30, and 45-week-old wild-type and Tgβ3 rats concluded that endothelial dysfunction could be a cause of HFpEF development.

Vascular Senescence in Cardiovascular and Metabolic Diseases

It is clear that cellular senescence drives various pathological changes associated with aging, and further investigation into the role of this biological process in age-related disorders and discovery of senolytic compounds are important fields for future exploration.

The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction

This review summarizes current concepts about a microvascular inflammation in hypertrophied myocardium and provides a translational perspective of the anti-inflammatory and immunomodulatory approaches in HFpEF.


Current knowledge of SIRT3 in EC metabolic reprograming, EC/pericyte interactions, coronary microvascular dysfunction, and HFpEF is summarized.

Cellular Senescence in Cardiovascular Diseases: A Systematic Review

The mechanisms underlying cellular senescence are discussed and the involvement of senescent cardiovascular cells (including cardiomyocytes, endothelial cells, vascular smooth muscle cells, fibroblasts/myofibro Blasts and T cells) in age-related cardiovascular diseases are described.

Arterial Remodeling and Dysfunction in the ZSF1 Rat Model of Heart Failure With Preserved Ejection Fraction.

Functional, molecular, and structural disturbances of central vessels and their potentially underlying pathways were newly characterized in experimental heart failure with preserved ejection fraction rendering the ZSF1 obese rat model suitable for preclinical testing.

Heart Failure Syndrome With Preserved Ejection Fraction Is a Metabolic Cluster of Non-resolving Inflammation in Obesity

Information is compiled on obesity-directed macrophage dysfunction that coincide with metabolic defects in HFpEF and the advances observed with formyl peptide 2 (FPR2) receptor, a prime sensor that is important in inflammation-resolution signaling.

Aging and Cardiovascular Diseases: The Role of Cellular Senescence

The phenomenon of cellular senescence is described with emphasis to its link to oxidative stress during aging and its essential role on the pathology of the vascular system.



Diastolic dysfunction is associated with cardiac fibrosis in the senescence-accelerated mouse.

SAMP8 mice show increased fibrosis and diastolic dysfunction similar to those seen in humans with aging and may represent a suitable model for future mechanistic studies.

Senescence and Death of Primitive Cells and Myocytes Lead to Premature Cardiac Aging and Heart Failure

Abstract— Chronological myocardial aging is viewed as the inevitable effect of time on the functional reserve of the heart. Cardiac failure in elderly patients is commonly interpreted as an

High-intensity interval training attenuates endothelial dysfunction in a Dahl salt-sensitive rat model of heart failure with preserved ejection fraction.

Findings suggest heart failure patients with preserved left ventricular ejection fraction (HFpEF) induces endothelial dysfunction, but this is reversible by HIT, and HIT was able to attenuate both these functional and molecular alterations.

Age-associated pro-inflammatory adaptations of the mouse thoracic aorta.

A reduction in endothelial cell-mediated vasodilation in aged thoracic aortas of C57BL/6J mice was accompanied by a shift towards a pro-inflammatory state of the endothelium, associated with hypertrophy of vascular SMCs.

The roles of senescence and telomere shortening in cardiovascular disease

The 'senescence-associated secretory phenotype' of senescent cells exerts a wide range of autocrine and paracrine activities aimed at tissue repair but which also fuel degenerative and proliferative alterations that contribute to cardiovascular disease.

Animal models of heart failure with preserved ejection fraction

An overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models are provided.