Article

Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome

Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX 77843, USA.
AJP Heart and Circulatory Physiology (Impact Factor: 3.84). 12/2011; 302(3):H643-53. DOI: 10.1152/ajpheart.00606.2011
Source: PubMed

ABSTRACT

Numerous studies on metabolic syndrome (MetSyn), a cluster of metabolic abnormalities, have demonstrated its profound impact on cardiovascular and blood microvascular health; however, the effects of MetSyn on lymphatic function are not well understood. We hypothesized that MetSyn would modulate lymphatic muscle activity and alter muscularized lymphatic function similar to the impairment of blood vessel function associated with MetSyn, particularly given the direct proximity of the lymphatics to the chronically inflamed adipose depots. To test this hypothesis, rats were placed on a high-fructose diet (60%) for 7 wk, and their progression to MetSyn was assessed through serum insulin and triglyceride levels in addition to the expression of metabolic and inflammatory genes in the liver. Mesenteric lymphatic vessels were isolated and subjected to different transmural pressures while lymphatic pumping and contractile parameters were evaluated. Lymphatics from MetSyn rats had significant negative chronotropic effects at all pressures that effectively reduced the intrinsic flow-generating capacity of these vessels by ∼50%. Furthermore, lymphatics were remodeled to a significantly smaller diameter in the animals with MetSyn. Wire myograph experiments demonstrated that permeabilized lymphatics from the MetSyn group exhibited a significant decrease in force generation and were less sensitive to Ca(2+), although there were no significant changes in lymphatic muscle cell coverage or morphology. Thus, our data provide the first evidence that MetSyn induces a remodeling of collecting lymphatics, thereby effectively reducing their potential load capabilities and impairing the intrinsic contractility required for proper lymph flow.

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    • "Dilated collecting lymphatic vessels with a reduction in the frequency of contractions have been found in experimental models of inflammation and cancer [15], [19]. Similar to our current findings, a reduction in the contraction frequencies of the mesenteric collecting lymphatic vessels was found in a rat model of metabolic syndrome [20]. Since it is well established that obesity is associated with low-level inflammation, there may be direct effects of inflammatory cytokines on lymphatic vessels during obesity [10], [21]. "
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