Arterial hardening, also known as atherosclerosis, is the result of plaque buildup in the walls of arteries and over time can lead to cardiovascular complications, including heart attack, stroke, and peripheral vascular disease.
Atherosclerotic plaques typically develop in arterial regions with disrupted blood flow. While blood flow disturbances are known to alter endothelial gene expression and function, it is not clear how altered blood flow induces these changes in endothelial cells.
In this issue of the Journal of Clinical Investigation, Hanjoong Jo and colleagues at the Georgia Institute of Technology and Emory University present evidence that blood flow disturbances alter genome-wide methylation patterns in endothelial cells through the induction of the DNA methyltransferase DNMT.
Long-term epigenetic changes induced within the arterial endothelium may further promote atherosclerosis, and genes that are altered in response to disturbed flow represent potential therapeutic targets for limiting plaque formation.
TITLE: Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis http://www.jci.org/articles/view/74792
Protecting dopaminergic neurons from Parkinson's disease-associated degradation
A defining characteristic of Parkinson's disease (PD) is the prominent degeneration and loss of dopaminergic (DA) neurons within the substantia nigra pars compacta (SNpc) region of the brain; however, it is not clear why this population of DA neurons is preferentially targeted in PD.
In this issue of the Journal of Clinical Investigation, Huaibin Cai and colleagues at the National Institute on Aging identified a subpopulation of SNpc DA neurons lacking aldehyde dehydrogenase 1 (ALDH1A1) that are especially prone to degeneration and accumulation of cytotoxic levels of α-synuclein in a murine model of PD. Evaluation of PD patient and healthy brains revealed a reduction ALDH1A1 expression and reduced numbers of ALDH1A1-expressing DA neurons in the SNpc of PD patients.
In PD mice, deletion of Aldh1a1 exacerbated both the loss of DA neurons and α-synuclein aggregation. Expression of ALDH1A1 in cultured DA neurons from PD mice enhanced cell survival, preventing caspase-mediated cell death. Together, the results from this study suggest that reduced ALDA1A1 expression in PD DA neurons makes this population vulnerable to α-synuclein-mediated degeneration.
TITLE: Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation, http://www.jci.org/articles/view/72176?key=c584826fe7a1ee622ffd