The ebb and flow of cardiac lymphatics: a tidal wave of new discoveries

Abstract

The heart is imbued with a vast lymphatic network which is responsible for fluid homeostasis and immune cell trafficking. Disturbances in the forces that regulate microvascular fluid movement can result in myocardial edema, which has pro-fibrotic and pro-inflammatory consequences and contributes to cardiovascular dysfunction. This review explores the complex relationship between cardiac lymphatics, myocardial edema and cardiac disease. It covers the revised paradigm of microvascular forces and fluid movement around the capillary, as well as the arsenal of preclinical tools and animal models used to model myocardial edema and cardiac disease. Clinical studies of myocardial edema and their prognostic significance are examined in parallel to the recent elegant animal studies discerning the pathophysiological role and therapeutic potential of cardiac lymphatics in different cardiovascular disease models. This review highlights the outstanding questions of interest to both basic scientists and clinicians regarding the roles of cardiac lymphatics in health and disease.

Sodium, Interstitium, Lymphatics and Hypertension—A Tale of Hydraulics

“…Similar to the kidneys, the development of interstitial edema impacts systolic and diastolic myocardial function and elicits an increase in cardiac lymphatic transport as a compensatory mechanism. 95 This response, meant to limit cardiac injury and fibrosis, appears to involve an acute dilatory and a chronic growth phase. 96 However, at variance with other organs, cardiac lymphatic collectors lack lymphatic muscle coverage.…”

Cardiac Lymphangiogenesis in CVDs

“…10 Experimental work has demonstrated that cardiac lymphangiogenesis is reactivated in CVDs, such as atherosclerosis and MI, as well as in pathological cardiac hypertrophy, resulting from pressure overload induced by Ang II (angiotensin II) or by surgical transaortic constriction. 1,2,5,[11][12][13] Considerable lymphatic remodeling occurs after MI, as the initial destruction of lymphatics in the scar area is followed by recruitment of inflammatory cells that stimulate an aberrant lymphangiogenic response. This generates strikingly dilated, poorly functional vessels that appear to be insufficient for limiting local inflammation or edema in the scar.…”

Role of the Lymphatics in Cardiac Disease

“…76 First, HF with reduced ejection fraction is caused primarily by an insult damaging the cardiac tissue and induces a vicious cycle of injury due to general fluid retention that increases the systemic pressure, exacerbating the underlying myocardial edema and further reducing myocardial performance. 77 HF with preserved ejection fraction, however, is caused by an underlying metabolic dysfunction (eg, obesity, diabetes, and hypertension) and has been shown to cause lymphatic dilation and increasing vessel permeability in both preclinical and clinical studies. 78 Indeed, a recent study of skin biopsies from patients with HF with preserved ejection fraction identified lymphatic vessel rarefaction and dilation reflecting impaired drainage, thus exacerbating the condition.…”