The Dual Role of Surfactant Protein-D in Vascular Inflammation and Development of Cardiovascular Disease

Abstract

Cardiovascular disease (CVD) is responsible for 31% of all global deaths. Atherosclerosis is the major cause of cardiovascular disease and is a chronic inflammatory disorder in the arteries. Atherosclerosis is characterized by the accumulation of cholesterol, extracellular matrix, and immune cells in the vascular wall. Recently, the collectin surfactant protein-D (SP-D), an important regulator of the pulmonary immune response, was found to be expressed in the vasculature. Several in vitro studies have examined the role of SP-D in the vascular inflammation leading to atherosclerosis. These studies show that SP-D plays a dual role in the development of atherosclerosis. In general, SP-D shows anti-inflammatory properties, and dampens local inflammation in the vessel, as well as systemic inflammation. However, SP-D can also exert a pro-inflammatory role, as it stimulates C-C chemokine receptor 2 inflammatory blood monocytes to secrete tumor necrosis-factor α and increases secretion of interferon-γ from natural killer cells. In vivo studies examining the role of SP-D in the development of atherosclerosis agree that SP-D plays a proatherogenic role, with SP-D knockout mice having smaller atherosclerotic plaque areas, which might be caused by a decreased systemic inflammation. Clinical studies examining the association between SP-D and cardiovascular disease have reported a positive association between circulatory SP-D level, carotid intima-media thickness, and coronary artery calcification. Other studies have found that circulatory SP-D is correlated with increased risk of both total and cardiovascular disease mortality. Both in vitro, in vivo, and clinical studies examining the relationship between SP-D and CVDs will be discussed in this review.

A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19

“…Furthermore, SP-D plasma level is considered to be a putative biomarker for pulmonary disease ( 325 , 417 ), such as acute airway inflammation ( 418 ), or exacerbation of COPD ( 419 ). Importantly, it was also described as a biomarker of cardiovascular diseases ( 420 , 421 ) or atherosclerosis ( 325 ). Hence, comparing SP-D plasma level in non-critical vs. critical patients could indicate if SP-D could be an additional biomarker of COVID-19 disease severity.…”

Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

“…The most prevalent SP-D structure, the dodecameric conformation, seems to possess anti-inflammatory properties, while the trimeric or monomeric isoforms, are believed to have pro-inflammatory properties, when SP-D is in an inflammatory or more acidic environment (86)(87)(88)(89)(90)(91). Surfactant is mainly produced in the lung, but surfactant mRNA and protein have also been identified in heart, arteries, kidney, and other organs (56,86,92) (Figures 3, 4); and SP-A and SP-D seem to modulate the immune response by preventing excessive inflammation, as found in the cytokine storm caused by COVID-19, that can potentially damage the lungs and impair gas exchange (55). Pulmonary SP-D production can be enhanced by tumor necrosis factor-a (TNF-a)-mediated induction of IL-13 (90) (Figure 3).…”

Elevated Blood Glucose Levels as a Primary Risk Factor for the Severity of COVID-19

“…Furthermore SP-D plasma level is considered to be a putative biomarker for pulmonary disease (324, 414), such as acute airway inflammation (415), or exacerbation of COPD (416). Importantly, it was also described as a biomarker of cardiovascular diseases (417, 418) or atherosclerosis (324). Hence, comparing SP-D plasma level in non-critical versus critical patients could indicate if SP-D could be an additional biomarker of COVID-19 disease severity.…”