Vascular aging (VA) is the progressive vascular remodeling and alteration of vascular structure that accompanies biological aging. VA results in an increase in artery stiffness, accompanied by impairment of endothelial regeneration and shortening of leukocyte telomere length (LTL). The progress of VA in early age strongly predicts the occurrence of CVD, the leading cause of death in old age. This progress is determined in part by genetic factors, with effects modifiable by exposure to various non-genetic factors. The overall objective of this proposal is to identify genetic components with modest-to-large longitudinal effects on the progress of VA from childhood, and to investigate the association of genetic components with circulating endothelial progenitor cells (EPCs) and leukocyte telomere length (LTL) that represent endothelial regeneration and biological aging respectively.
Our specific aims are to: (1) Identify genomic linkage regions and candidate genes underlying VA. The hypotheses are that one or more chromosome regions exert modest-to-large, heritable genetic effects on VA phenotypes from early childhood, and that some candidate genes exert modest-to-large effects but lack detectable heritability. (2) Determine common and rare effect variants at the genomic linkage regions and candidate genes identified in Specific Aim 1 that are associated with VA, endothelial regeneration and biological aging. The hypotheses are that genetic determinants underlying VA phenotypes are related to circulating EPCs and LTL, and rare functional variants in five important candidate genes are associated with longitudinal VA phenotypes in the upper and lower 5% of BHS participants. (3) Validate significant findings from Specific Aim 2 in a replication sample. The hypothesis is that the findings of common and rare effect variants will be repeated in a random populationbased sample and are associated with healthy aging. It is expected that identification of effect variants underlying VA will be important for defining genetic predisposition to vascular aging or healthy aging later in life.

Public Health Relevance

The proposed study has important clinical and public health implications. It will provide a more complete understanding of the link between vascular aging in early life and CVD effects and healthy aging in later life. This will thus provide us the means for devising strategies to prevent VA and increase the chances of living to a successful old age.

National Institute of Health (NIH)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Tulane University
New Orleans
United States
Zip Code
Sweat, Richard S; Sloas, David C; Murfee, Walter L (2014) VEGF-C induces lymphangiogenesis and angiogenesis in the rat mesentery culture model. Microcirculation 21:532-40
Yoshida, Tadashi; Friehs, Ingeborg; Mummidi, Srinivas et al. (2014) Pressure overload induces IL-18 and IL-18R expression, but markedly suppresses IL-18BP expression in a rabbit model. IL-18 potentiates TNF-?-induced cardiomyocyte death. J Mol Cell Cardiol 75:141-51
Yoshida, Tadashi; Huq, Tashfin S; Delafontaine, Patrice (2014) Angiotensin type 2 receptor signaling in satellite cells potentiates skeletal muscle regeneration. J Biol Chem 289:26239-48
Kim, Sangkyu; Welsh, David A; Ravussin, Eric et al. (2014) An elevation of resting metabolic rate with declining health in nonagenarians may be associated with decreased muscle mass and function in women and men, respectively. J Gerontol A Biol Sci Med Sci 69:650-6
Lynch, Kristen M; Ahsan, Tabassum (2014) Correlating the effects of bone morphogenic protein to secreted soluble factors from fibroblasts and mesenchymal stem cells in regulating regenerative processes in vitro. Tissue Eng Part A 20:3122-9
Luo, Fayong; Zhuang, Yan; Sides, Mark D et al. (2014) Arsenic trioxide inhibits transforming growth factor-?1-induced fibroblast to myofibroblast differentiation in vitro and bleomycin induced lung fibrosis in vivo. Respir Res 15:51
Stapor, Peter C; Sweat, Richard S; Dashti, Derek C et al. (2014) Pericyte dynamics during angiogenesis: new insights from new identities. J Vasc Res 51:163-74
Zsombok, Andrea (2013) Vanilloid receptors--do they have a role in whole body metabolism? Evidence from TRPV1. J Diabetes Complications 27:287-92
Jiang, Yanyan; Gao, Hong; Krantz, Amanda M et al. (2013) Reduced GABAergic inhibition of kidney-related PVN neurons in streptozotocin-treated type 1 diabetic mouse. J Neurophysiol 110:2192-202
Stapor, Peter C; Azimi, Mohammad S; Ahsan, Tabassum et al. (2013) An angiogenesis model for investigating multicellular interactions across intact microvascular networks. Am J Physiol Heart Circ Physiol 304:H235-45

Showing the most recent 10 out of 13 publications