Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome
Identifieur interne : 002F23 ( Pmc/Checkpoint ); précédent : 002F22; suivant : 002F24Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome
Auteurs : Scott D. Zawieja ; Wei Wang ; Xin Wu ; Zhanna V. Nepiyushchikh ; David C. Zawieja ; Mariappan MuthuchamySource :
- American Journal of Physiology - Heart and Circulatory Physiology [ 0363-6135 ] ; 2011.
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 Ca2+, 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.
Url:
DOI: 10.1152/ajpheart.00606.2011
PubMed: 22159997
PubMed Central: 3353801
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<front><div type="abstract" xml:lang="en"><p>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<sup>2+</sup>
, 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.</p>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Physiol Heart Circ Physiol</journal-id>
<journal-id journal-id-type="iso-abbrev">Am. J. Physiol. Heart Circ. Physiol</journal-id>
<journal-id journal-id-type="hwp">ajpheart</journal-id>
<journal-id journal-id-type="pmc">ajpheart</journal-id>
<journal-id journal-id-type="publisher-id">AJPHEART</journal-id>
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<issn pub-type="epub">1522-1539</issn>
<publisher><publisher-name>American Physiological Society</publisher-name>
<publisher-loc>Bethesda, MD</publisher-loc>
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<article-id pub-id-type="doi">10.1152/ajpheart.00606.2011</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vascular Biology and Microcirculation</subject>
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<title-group><article-title>Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zawieja</surname>
<given-names>Scott D.</given-names>
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<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Wei</given-names>
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</contrib>
<contrib contrib-type="author"><name><surname>Wu</surname>
<given-names>Xin</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Nepiyushchikh</surname>
<given-names>Zhanna V.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Zawieja</surname>
<given-names>David C.</given-names>
</name>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Muthuchamy</surname>
<given-names>Mariappan</given-names>
</name>
</contrib>
<aff>Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas</aff>
</contrib-group>
<author-notes><corresp>Address for reprint requests and other correspondence: M. Muthuchamy,
<addr-line>Dept. of Systems Biology and Translational Medicine, Texas A&M Health Science Center College of Medicine, 336 Reynolds Medical Bldg., College Station, TX 77843</addr-line>
(e-mail: <email>marim@tamu.edu</email>
).</corresp>
</author-notes>
<pub-date pub-type="ppub"><day>1</day>
<month>2</month>
<year>2012</year>
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<pub-date pub-type="epub"><day>9</day>
<month>12</month>
<year>2011</year>
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<pub-date pub-type="pmc-release"><day>1</day>
<month>2</month>
<year>2013</year>
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<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
. </pmc-comment>
<volume>302</volume>
<issue>3</issue>
<fpage>H643</fpage>
<lpage>H653</lpage>
<history><date date-type="received"><day>17</day>
<month>6</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>3</day>
<month>12</month>
<year>2011</year>
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<permissions><copyright-statement>Copyright © 2012 the American Physiological Society</copyright-statement>
<copyright-year>2012</copyright-year>
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<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zh400312000643.pdf"></self-uri>
<abstract><p>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<sup>2+</sup>
, 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.</p>
</abstract>
<kwd-group><kwd>chronotropic effect</kwd>
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<kwd>calcium sensitivity</kwd>
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<name sortKey="Wang, Wei" sort="Wang, Wei" uniqKey="Wang W" first="Wei" last="Wang">Wei Wang</name>
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