Microvascular perfusion heterogeneity contributes to peripheral vascular disease in metabolic syndrome.
A major challenge facing public health is the increased incidence and prevalence of the metabolic syndrome, a clinical condition characterized by excess adiposity, impaired glycaemic control, dyslipidaemia and moderate hypertension. The greatest concern for this syndrome is the profound increase in risk for development of peripheral vascular disease (PVD) in afflicted persons. However, ongoing studies suggest that reductions in bulk blood flow to skeletal muscle may not be the primary contributor to the premature muscle fatigue that is a hallmark of PVD. Compelling evidence has been provided suggesting that an increasingly spatially heterogeneous and temporally stable distribution of blood flow at successive arteriolar bifurcations in metabolic syndrome creates an environment where a large number of the pre-capillary arterioles have low perfusion, low haematocrit, and are increasingly confined to this state, with limited ability to adapt perfusion in response to a challenged environment. Single pharmacological interventions are unable to significantly restore function owing to a divergence in their spatial effectiveness, although combined therapeutic approaches to correct adrenergic dysfunction, elevated oxidant stress and increased thromboxane A2 improve perfusion-based outcomes. Integrated, multi-target therapeutic interventions designed to restore healthy network function and flexibility may provide for superior outcomes in subjects with metabolic syndrome-associated PVD.
Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, WV, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, WV, USA.
Jefferson C
JC
Frisbee
Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, WV, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, WV, USA.
Adam G
AG
Goodwill
Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, WV, USA.|Department of Health Policy, Management and Leadership, West Virginia University Health Sciences Center, Morgantown, WV, USA.
Stephanie J
SJ
Frisbee
Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, WV, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, WV, USA.
Joshua T
JT
Butcher
Novartis Institutes for BioMedical Research, Drug Metabolism and Pharmacokinetics, East Hanover, NJ, USA.
Fan
F
Wu
Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, WV, USA.|Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, WV, USA.
Paul D
PD
Chantler
D000818:Animals; D006801:Humans; D024821:Metabolic Syndrome / Q000150:complications*; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D013931:Thromboxanes / Q000378:metabolism
D013931:Thromboxanes