SERPINA1 and cardiovascular disorder: The mechanisms that link AATD or augmentation therapy with decreased frequency of cardiovascular disease are speculative and may be related to the pleiotropic activities of AAT [30, 31] These activities might include i) loss of vascular elastic recoil and decreased resistance due to excess activity of elastase; ii) upregulation and release of angiopoietin-like protein 4 (Angptl4) by AAT in complex with fatty acids [32–34].; iii) decreased production of inflammatory cytokines, such as TNF-α and IL-1β by AAT [35].