The Present and Future
State-of-the-Art Review
The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels

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Abstract

Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients. Next, the authors summarize the current understanding of the mechanisms implicated in cardiovascular aging, and the potential for targeting novel pathways implicated in endothelial dysfunction, mitochondrial oxidative stress, chromatin remodeling, and genomic instability. Lastly, the authors consider critical aspects of vascular repair, including autologous transplantation of bone marrow-derived stem cells in elderly patients.

Key Words

arterial stiffness
endothelium
epigenetics
stem cells

Abbreviations and Acronyms

BM
bone marrow
CAC
circulating angiogenic cell
CHD
coronary heart disease
CI
confidence interval
COX
cyclooxygenase
CV
cardiovascular
CVD
cardiovascular disease
eNOS
endothelial nitric oxide synthase
EPC
endothelial progenitor cell
HFpEF
heart failure with preserved ejection fraction
LTL
leukocyte telomere length
LV
left ventricular
MI
myocardial infarction
MMP
matrix metalloproteinase
NF-κB
nuclear factor kappa-B
OR
odds ratio
PBMC
peripheral blood mononuclear cell
RAAS
renin-angiotensin-aldosterone system
ROS
reactive oxygen species
RR
relative risk
TGF
transforming growth factor
TNF
tumor necrosis factor
VSMC
vascular smooth muscle cell
wtTTR
wild-type transthyretin

Cited by (0)

The present work was supported by the Swiss National Science Foundation (Drs. Lüscher and Camici) and the Alfred and Annemarie von Sick Grants for Translational and Clinical Research Cardiology and Oncology (Dr. Camici), an unrestricted research grant by Pfizer, Inc. (Dr. Lüscher), the Foundation for Cardiovascular Research–Zurich Heart House and the U.S. National Institutes of Health (RO1 HL080472), and from the RRM Charitable Fund (Dr. Libby). Drs. Paneni and Camici are recipients of a Sheikh Khalifa's Foundation Assistant Professorship at the Faculty of Medicine, University of Zurich. Dr. Libby has been an unpaid consultant for Amgen, AstraZeneca, Esperion Therapeutics, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Merck & Co., Novartis, Pfizer, Sanofi-Regeneron, Takeda Pharmaceuticals, and XBiotech; served as a scientific advisory board member for Amgen, Athera Biotechnologies, Corvidia Therapeutics, DalCor Pharmaceuticals, Interleukin Genetics, Kowa Pharmaceuticals, Medimmune, and Novartis; and has received lab funding from Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.