The year in cardiology: aorta and peripheral circulation

Abstract

to qualify atherosclerotic disease of the lower extremity arteries and carotid arteries. In the current article and in line with the European Society of Cardiology (ESC) guidelines, (4) we have stringently used the specific terms lower extremity arterial disease (LEAD) and have reserved PAD as the umbrella term encompassing all arterial diseases other than relating to the aorta and coronaries. VASCULAR BIOLOGY/TRANSLATIONAL RESEARCHThe extent to which genetic factors contribute to PAD development and if they are shared or distinct between LEAD, cerebral, and coronary arteries are largely unknown. In a genome-wide association study in the Million Veteran Program, ~32 million DNA sequence variants were tested for PAD (31 307 cases, 211 753 controls) and combined with electronic health records. (5) The results were replicated in an independent sample from the UK Biobank. They identified 19 LEAD loci (18 not previously reported): 11 loci were associated with disease in 3 vascular beds (coronary, cerebral, and lower extremity), including LDLR, LPL, and Lp(a) (Figure 1); 4 loci appeared to be specific for LEAD, including F5 p.R506Q (Factor V Leiden variant), highlighting the pathogenic role of thrombosis in LEAD and supporting Factor Xa inhibition as a therapeutic strategy.Despite the fact that numerous long non-coding RNAs (lncRNA) have been identified, only a few of them have been studied with respect to endothelial cell homeostasis or vascular disease development. One of them, the pro-angiogenic lncRNA MANTIS, may be clinically relevant in carotid disease. (6) In fact, the protective effects of laminar flow and statins are, at least in part, attributed to the expression of MANTIS. The mechanisms involve epigenetic rearrangements and the transcription factors Krüppel-like factor 2 and 4. As induction of MANTIS mimics the beneficial effects of statins on endothelial function, the authors proposed that strategies to increase MANTIS might improve vascular function in patients not responding to statin therapy.