Emerging trends in the pathophysiology of lymphatic contractile function

Abstract

Lymphatic contractile dysfunction is central to a number of pathologies that affect millions of people worldwide. Due to its critical role in the process of inflammation, a dysfunctional lymphatic system also compromises the immune response, further exacerbating a number of inflammation related diseases. Despite the critical physiological functions accomplished by the transport of lymph, a complete understanding of the contractile machinery of the lymphatic system lags far behind that of the blood vasculature. However, there has been a surge of recent research focusing on different mechanisms that underlie both physiological and pathophysiological aspects of lymphatic contractile function. This review summarizes those emerging paradigms that shed some novel insights into the contractile physiology of the lymphatics in normal as well as different disease states. In addition, this review emphasizes the recent progress made in our understanding of various contractile parameters and regulatory elements that contribute to the normal functioning of the lymphatics.

Lymphatic pumping: mechanics, mechanisms and malfunction

“…Like vascular smooth muscle, lymphatic muscle contraction is regulated primarily by the balance of myosin light chain kinase (MLCK)/myosin light chain phosphatase (MLCP) activity controlling myosin light chain phosphorylation (reviewed in Chakraborty et al . a ). Lymphatic vessels resemble arterioles in that they develop basal tone and exhibit myogenic constriction to pressure elevation (Davis et al .…”

“…The outer edges of the fluorescent border demarcate the inner diameter of the vessel, which becomes clear when the fluorescence ( Lymphatic muscle is non-striated and usually classified as vascular smooth muscle, but it shares biochemical and functional characteristics with both vascular and cardiac muscle (von der Weid & Zawieja, 2004). Like vascular smooth muscle, lymphatic muscle contraction is regulated primarily by the balance of myosin light chain kinase (MLCK)/myosin light chain phosphatase (MLCP) activity controlling myosin light chain phosphorylation (reviewed in Chakraborty et al 2015a). Lymphatic vessels resemble arterioles in that they develop basal tone and exhibit myogenic constriction to pressure elevation (Davis et al 2009).…”

Macrophage alterations within the mesenteric lymphatic tissue are associated with impairment of lymphatic pump in metabolic syndrome

“…Lymphatic collecting vessels exhibit both sensitive regulation of vessel tone and also rhythmic large contractions that can be described in similar terms as the cardiac cycle . Physical stimuli such as shear stress (flow) and stretch (pressure), both have significant roles in the regulation of lymphatic contractions . In humans, the intrinsic contractions are responsible for transporting up to two‐third of lymph from the lower extremities, and failure of the lymphatic system results in a chronic and progressive disease called lymphedema …”

“…2 Physical stimuli such as shear stress (flow) and stretch (pressure), both have significant roles in the regulation of lymphatic contractions. 3 In humans, the intrinsic contractions are responsible for transporting up to two-third of lymph from the lower extremities, 4 and failure of the lymphatic system results in a chronic and progressive disease called lymphedema. 5 While genetic malformations are linked with primary lymphedema, the majority of lymphedema cases are secondary to other complications.…”

Hyperglycemia‐ and hyperinsulinemia‐induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle

“…The lymphatic system, with its intrinsic physiologic functions in cellular homeostasis, immune cell trafficking, and lipid absorption (11–13), contributes significantly to the pathogenesis of metabolic disorders (14–17). We have demonstrated that lymphatic vessels from MetSyn rats exhibit impaired intrinsic contractile activity (18, 19).…”