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Near Term Prospects for Ameliorating Cardiovascular Aging

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Book cover The Future of Aging

Abstract

Cardiovascular disease (CVD) is the leading cause of death in the United States and affects 1 out of every 3 American adults. The most important predictor of CVD is age and this is likely from myriad factors including increased exposure to known cardiovascular risk factors, increased time for disease to occur, and age-related structural and functional changes of the heart and vascular network. These age-related alterations may be further exacerbated when combined with traditional CVD risk factors and provide an even more suitable milieu for atherosclerosis to develop.

Dyslipidemia management has been a major area of focus in atherosclerosis prevention. While interventions to optimize serum cholesterol profiles have made significant contributions in reducing coronary heart disease (CHD), many patients with normal lipid levels still continue to have significant CHD and crippling cardiac events. HDL, widely touted as the “good cholesterol”, is protective against atherosclerosis when it is healthy. The best-known antiatherogenic property of HDL is its ability to promote cholesterol efflux from cells. In certain diseases or stress conditions, the normal functions of HDL can be disrupted and the HDL may actually promote atherogenesis. The ability of HDL to prevent or promote atherogenesis can be assessed using a parameter called the HDL-inflammatory index.

A new class of peptides that emulate the action of the major HDL protein apolipoprotein (apo)A-I have been shown to be effective in improving the function of dysfunctional HDL by changing it from pro-inflammatory to anti-inflammatory in quality. The next generation of therapeutics may include compounds such as apoA-I mimetic peptides that have been found to have significant effect on various aspects of cardiovascular pathology including atherosclerosis as well as several non-atherosclerotic diseases. ApoA-I mimetic peptides may be effective in ameliorating cardiovascular aging and prove to be a beneficial adjunct to the current strategy of battling CVD.

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Abbreviations

ABCA1:

ATP-binding cassette transporter A1

AHA:

American Heart Association

apo:

apolipoprotein

CCA:

cell co-culture assay

CETP:

cholesteryl ester transfer protein

CFA:

cell-free assay

CHD:

coronary heart disease

CHF:

congestive heart failure

CVD:

cardiovascular disease

DM:

diabetes mellitus

eNOS:

endothelial NO synthase

EPC:

endothelial progenitor cell

HDL:

high-density lipoprotein

HDL-C:

HDL cholesterol level

HO-1:

hemeoxygenase-1

HTN:

hypertension

ICAM-1:

intercellular adhesion molecule-1

IL:

interleukin

JNC 7:

The Seventh Report of the Joint National Committee

LCAT:

lecithin cholesterol acyltransferase

LDL:

low-density lipoprotein

LDL-C:

LDL cholesterol level

LDLR:

LDL receptor

LOOH:

lipid hydroperoxide

LV:

left ventricular

MCA:

monocyte chemotactic activity

MCP-1:

monocyte chemoattractant protein-1

MIP-1α:

macrophage inflammatory protein-1α

MM-LDL:

minimally-modified LDL

MWM:

Morris Water Maze

NCEP ATP III:

National Cholesterol Education Panel, Adult Treatment Panel III

NO:

nitric oxide

OX-LDL:

oxidized LDL

PAF-AH:

platelet activating factor acetylhydrolase

PLTP:

phospholipid transfer protein

PON:

paraoxonase

RA:

rheumatoid arthritis

SAA:

serum amyloid A

SLE:

systemic lupus erythematosus

sPLA2:

secretory phospholipase A2

SSc:

scleroderma, or systemic sclerosis

T-CAT:

T-maze continuous alternation task

Tsk-/+:

tight skin

VCAM-1:

vascular cell adhesion molecule-1

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Authors and Affiliations

  1. Hospital Medicine Program, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Span 2, Boston, MA, 02215, USA

    Roger Yu

  2. David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA

    Kaveh Navab

  3. Department of Cardiology, UCLA Medical Center, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA

    Mohamad Navab

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  1. Roger Yu
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  2. Kaveh Navab
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  3. Mohamad Navab
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Correspondence to Roger Yu .

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  1. Intervene Biomedical, LLC, Box 478, Norco, CA, 92860, USA

    Gregory M. Fahy

  2. BioTime, Inc., 1301 Harbor Bay Parkway, Alameda, CA, 94502, USA

    Michael D. West

  3. Institute of Molecular Biology Department of Chemistry and Biochemistry Young Hall, University of California, Los Angeles, CA, 90095-1569, USA

    L. Stephen Coles

  4. Critical Care Research, Inc., 10743 Civic Center Drive, Rancho Cucamonga, CA, 91730, USA

    Steven B. Harris

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Yu, R., Navab, K., Navab, M. (2010). Near Term Prospects for Ameliorating Cardiovascular Aging. In: Fahy, G.M., West, M.D., Coles, L.S., Harris, S.B. (eds) The Future of Aging. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3999-6_8

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