Journal
JOURNAL OF VASCULAR RESEARCH
Volume 50, Issue 3, Pages 177-185Publisher
KARGER
DOI: 10.1159/000350528
Keywords
Heart failure; Resistance arteries; Total peripheral resistance; Myogenic response; Tumor necrosis factor-alpha; Sphingosine-1-phosphate
Categories
Funding
- Ontario Graduate Scholarship - Science and Technology
- Heart and Stroke Foundation of Ontario - Queen Elizabeth II Scholarship
- Canadian Institutes of Health Research [MOP-84402]
- Canadian Foundation for Innovation
- Ontario Research Fund [11810]
- Canadian Stroke Network
- Heart and Stroke Foundation of Ontario New Investigator Award
- University of Toronto
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Heart failure (HF) is hallmarked by an increase in total peripheral resistance (TPR) that compensates for the drop in cardiac output. While initially allowing for the maintenance of mean arterial pressure at acceptable levels, the long-term upregulation of TPR is prone to compromise cardiac performance and tissue perfusion, and to ultimately accelerate disease progression. Augmented vasoconstriction of terminal arteries, the site of TPR regulation, is cooperatively driven by mechanisms such as: (i) endothelial dysfunction, (ii) increased sympathetic activity and (iii) enhanced pressure-induced myogenic responsiveness. Herein, we review emerging evidence that the increase in myogenic responsiveness is central to the long-term elevation of TPR in HF. On a molecular level, this augmented intrinsic response is governed by an activation of the tumor necrosis factor-alpha (TNF-alpha)/sphingosine-1-phosphate signaling axis in microvascular smooth muscle cells. The beneficial effect of TNF-alpha scavenging strategies on tissue perfusion in HF mouse models adds to the gaining momentum to revisit the use of anti-TNF-alpha treatment modalities in discrete HF patient populations. Copyright (C) 2013 S. Karger AG, Basel
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