High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

Abstract

Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of ALI, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin‐1‐dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone

“…One of the main effects of this resveratrol‐derived drug is the increase in APOA1 transcription. An anti‐tumorigenic activity of this lipoprotein has already been described against melanoma (Zamanian‐Daryoush et al ., a) as well showing a protective role against the development of a variety of lung diseases, including lung cancer (Gordon et al ., ). Moreover, several studies have shown that APOA1 levels can be considered a biomarker with reduced plasma levels in patients with early stage ovarian cancer compared with normal individuals (Clarke et al ., ; Kim et al ., ; Kozak et al ., ; Moore et al ., ).…”

HER2 signaling regulates the tumor immune microenvironment and trastuzumab efficacy

“…19 Subsequently, the IFN-γ produced by recruited stimulated lymphocytes, which has been described to be crucial for Th1 immunity and trastuzumab response, 26 would in turn induce CXCLs in tumor cells followed by improved T cell-trafficking and maintenance of immune-enriched TME. Although tumor antigenicity derived from a high mutational burden, as demonstrated in patients with melanoma and lung cancer who respond to immune-checkpoint inhibitors, 27-29 may also explain the infiltration of HER2+ BCs by adaptive immune cells, the low mutational burden of BCs compared to melanoma 30 and the lack of association between the amount of neoantigens and TIL count or trastuzumab activity in tumors from patients enrolled in the FinHer trial 31 do not support this possibility. Considering that CXCLs and HER2 mRNA levels are significantly positively correlated in HER2+ BC samples and in our in vitro models, it could be hypothesized that these molecules are co-regulated in trastuzumab responsive HER2-addicted tumors, the subgroup with the highest HER2 transcription.…”

Association Between Pretreatment Serum Apolipoprotein A1 and Prognosis of Solid Tumors in Chinese Population: A Systematic Review and Meta-Analysis

“…Extensive studies have shown that an abnormal level of lipid profile may influence carcinogenesis and is closely linked to tumor progression [12]. Cholesterol synthesis is raised in cancer cells compared with normal cells, as tumor cells require excess cholesterol and intermediates of the cholesterol biosynthesis pathway to sustain a high level of proliferation [13].…”