Molecular and functional analyses of the contractile apparatus in lymphatic muscle

Muthuchamy, Mariappan; Gashev, Anatoliy A.; Boswell, Niven; Dawson, Nancy S.; Zawieja, David C.

doi:10.1096/fj.02-0626fje

Cited by 166 publications

(196 citation statements)

References 38 publications

(49 reference statements)

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“…Our previous studies demonstrated regional heterogeneity in the contractile behavior of lymphatic vessels. 10,13,25 Our current studies provided the first evidence of regionally different influence of aging on different lymphatic networks. To illustrate such conclusions, we compared isolated MLV data with published data 4 obtained from experiments utilizing isolated rat TD segments from similar groups of adult (9-mo old) and aged (24-mo old) F-344 rats and treated with similar experimental conditions.…”

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confidence: 55%

Aged Lymphatic Contractility: Recent Answers and New Questions

Gashev

Chatterjee

2013

Lymphatic Research and Biology

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An overview is presented of recent findings related to biology of aging of the lymph transport system. The authors discuss recently obtained data on the aging-associated alterations of lymphatic contractility in thoracic duct and mesenteric lymphatic vessels; on comparisons of function of aged mesenteric lymphatic vessels in situ versus isolated specimens and important conclusions which arose from these studies; on aging-associated changes in functional status of mast cells located close to aged mesenteric lymphatic vessels; on evidence of presence of oxidative stress in aged lymphatic vessels and changes in arrangement of muscle cells in their walls. The authors conclude that future continuation of the research efforts in this area is necessary and will be able to provide not only novel fundamental knowledge on the biology of lymphatic aging, but also will create solid foundation for the subsequent developments of lymphatic-oriented therapeutic interventions in many diseases of the elderly.T he major task of the lymphatic system is lymph transport. This system of initial capillaries, transporting vessels, and nodes is designed to transport fluid, soluble molecules, and immune cells from the interstitium through the lymph nodes to the central veins. This system also provides the transportation route for inflammatory mediators, the products of tissue injury/destruction, foreign substances, and tumor cells. Dysfunctional lymph transport can result in a wide range of disturbances, including edema, altered immune cell trafficking, depressed immune function, and impaired lipid metabolism. The lack of knowledge on how aging affects lymphatic vessels certainly contributes to the situation when researchers and clinicians ignore lymph transport-related components of various diseases. Thus, investigation of the mechanisms affecting lymphatic contractile function during aging are extremely important for ongoing attempts to better understand the lymphatic system and to discover the pathogenesis and effective treatment of various aging-associated disorders.Until recently, there were no published reports on systematic studies on aging-associated changes in the active lymph pumps. Due to the profound difficulty of measuring lymph flow in vivo, there are only a few reports demonstrating the measurements of reduced lymph flow in aged animals. [1][2][3] In particular, it was reported 3 that aging significantly decreases lymph flow from the main mesenteric lymph duct by *60% between ages of 3 and 22 mo in rats.During the last years, we obtained important functional and molecular evidence of the aging-associated alterations of contractility in lymphatic vessels, which already widened our knowledge on the biology of aged lymph flow. On the other hand, our recent studies raise new important questions that may link several diseases to impaired coordination between lymphatic function and function of other systems in the aged body. While this review provides some recent answers on current questions in biology of lymphatic aging,...

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confidence: 55%

Aged Lymphatic Contractility: Recent Answers and New Questions

Gashev

Chatterjee

2013

Lymphatic Research and Biology

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“…In this respect, the behavior of lymphatics and small veins resembles that of phasic visceral smooth muscle (29). Our previous molecular analyses of the contractile apparatus demonstrated that mesenteric lymphatic muscle appears to have more organized contractile elements and different expression levels of contractile proteins, especially myosin heavy chains and actin, than do mesenteric arteries (36). This distinctly different composition of lymphatic contractile machinery in mesenteric lymphatics as well as the composition of the extracellular connective tissue matrix (14,23,38) might also contribute to the differences in the active length-tension relationship between arterial, venous, and lymphatic vessels.…”

Section: H1948 Length-tension Relationships Of Arteries Veins Lymphmentioning

confidence: 95%

“…Furthermore, comparisons between arterial, venous, and lymphatic vessels in the same vasculature do not exist. A recent study (36) demonstrated that muscle cells in rat mesenteric lymphatics have unique contractile machinery composed of both smooth and striated muscle components. Rat mesenteric lymphatic vessels also exhibit contractile characteristics different from lymphatics in other regions of that species (18,19).…”

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confidence: 99%

Length-tension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation

Zhang

Gashev

Zawieja

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Zhang RZ, Gashev AA, Zawieja DC, Davis MJ. Lengthtension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation. Am J Physiol Heart Circ Physiol 292: H1943-H1952, 2007. First published December 15, 2005; doi:10.1152/ajpheart.01000.2005.-The passive and active length-tension relationships of isolated rat mesenteric lymphatics (ϳ150 m ID), and adjacent small arteries (ϳ240 m) and veins (ϳ275 m) were compared under isometric conditions using a wire myograph. About 60% of the lymphatic vessels developed spontaneous contractions in physiological saline solution at nominal preload. To maximally activate smooth muscle, 145 mM K ϩ ϩ 5 ϫ 10 Ϫ5 M norepinephrine was used for arteries, and 145 mM K ϩ ϩ 1 ϫ 10 Ϫ6 M substance P was used for lymphatics and veins. In response, arteries exhibited monotonic force development to a plateau level, whereas lymphatics and veins showed biphasic force development, consisting of a transient force peak followed by partial relaxation to a plateau over ϳ5 min. The passive and the active length-tension curves were similar in shape among all three vessels. However, the maximal active tension of arteries (3.4 Ϯ 0.42 mN/mm) was significantly greater than peak active tension (0.59 Ϯ 0.04 mN/mm) or plateau tension (0.20 Ϯ 0.04 mN/mm) in small veins and greater than peak active tension (0.34 Ϯ 0.02 mN/mm) or plateau tension (0.21 Ϯ 0.02 mN/mm) in lymphatics. Maximal active medial wall stress was similar between lymphatics and veins but was approximately fivefold higher in small arteries. For lymphatics, the pressure calculated from the optimal preload was significantly higher than that found previously in isobaric studies of isolated lymphatics, suggesting the capacity to operate at higher than normal pressures for increased responsiveness. Our results represent the first mechanical comparisons of arterial, venous, and lymphatic vessels in the same vasculature.

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“…We (37) have previously shown that lymphatic muscle is structurally composed of both smooth and striated muscle contractile elements and functionally shares similarities with both cardiac muscle and VSM. This correlates well with the unique functional aspects of both tonic and phasic lymphatic contractions.…”

Section: M) Immunohistochemical and Western Blot Analyses Of Pmlc20mentioning

confidence: 98%

Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity

Wang¹,

Nepiyushchikh²,

Zawieja³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Based on the well-established finding that the phosphorylation of myosin light chain 20 (MLC20) plays an essential role in blood vessel smooth muscle contraction, we investigated if phosphorylated MLC20 (pMLC20) would modulate the tonic and/or phasic contractions of lymphatic muscle. The effects of ML-7, a MLC kinase inhibitor (1-10 M), were tested on the contractile parameters of isolated and cannulated rat mesenteric lymphatics during their responses to the known modulators, pressure (1-5 cmH2O) and substance P (SP; 10 Ϫ7 M). Immunohistochemical and Western blot analyses of pMLC20 were also performed on isolated lymphatics. The results showed that 1) increasing pressure decreased both the lymphatic tonic contraction strength and pMLC20-to-MLC20 ratio; 2) SP increased both the tonic contraction strength and phosphorylation of MLC20; 3) ML-7 decreased both the lymphatic tonic contraction strength and pMLC20-to-MLC20 ratio; and 4) the increase in lymphatic phasic contraction frequency in response to increasing pressure was diminished by ML-7; however, the phasic contraction amplitude was not significantly altered by ML-7 either in the absence or presence of SP. These data provide the first evidence that tonic contraction strength and phasic contraction amplitude of the lymphatics can be differentially regulated, whereby the increase in MLC20 phosphorylation produces an activation in the tonic contraction without significant changes in the phasic contraction amplitude. Thus, tonic contraction of rat mesenteric lymphatics appears to be MLC kinase dependent. ML-7; lymphatic contraction; tonic contraction; phasic contraction THE LYMPHATIC SYSTEM plays essential roles by returning the protein-rich interstitial fluid to the blood circulation for fluid homeostasis, transporting lipids and lipid-soluble vitamins absorbed from the intestines to the circulation for nutrition, and distributing immune cells to the lymph nodes for defense against diseases. All of these vital functions rely on the contractile activities of the muscle cells residing in the lymphatic vessel wall. The muscular lymphatic vessels are composed of many basic structural and functional units called lymphangions, which are capable of exhibiting intrinsic contractile activities to propel lymph flow through the network of the lymphatic vessels. Although the classical influence of pressure and flow on lymphatic contractility has been well documented (14 -16, 24, 31, 37, 38, 51), the molecular mechanisms regulating the contractile activities of the lymphatic muscle are not well understood.Cardiac muscles and most vascular smooth muscles (VSMs) exercise their physiological functions by phasic and tonic contractions, respectively, whereas lymphatic muscle accomplishes its functions using both tonic and phasic contractions. In general, an increase in the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) is the primary mechanism that initiates muscle contraction, a mechanism shared by striated muscles and VSMs. In striated muscle, Ca 2ϩ binding to troponin C in...

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Molecular and functional analyses of the contractile apparatus in lymphatic muscle

Cited by 166 publications

References 38 publications

Aged Lymphatic Contractility: Recent Answers and New Questions

Aged Lymphatic Contractility: Recent Answers and New Questions

Length-tension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation

Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity

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