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96 conditions, to maintaining nuclear factor κB (NF ‐κB) / iNOS not activated.3 Recent evidence demonstrates that nM concentrations of NO re‐ leased by eNOS counteract the binding of NF‐ ‐κB to its promoter response element, thereby modulating the activation and translocation of NF ‐κB.4 On the other hand, NO generated by “healthy” eNOS inhibits NF ‐κB DNA binding through S ‐nitrosylation of the Cys 62 residue of p50 subunit, thereby maintaining NF ‐κB un‐ der subtoxic concentrations.4 The maintenance of this equilibrium between Cav‐1 / eNOS at one side and NF ‐κB / iNOS on the opposite side rep‐ resents the basis for the physiological regulation of vascular functionality. Yet, the disruption of this relationship leads to endothelial dysfunc‐ tion and vascular inflammation. This is con‐ firmed in the model used by Mierke et al,1 ob‐ tained by means of Cav‐1 / eNOS knockout mice. Beside the above‐mentioned evidence, sever‐ al aspects on the shift occurring at the level of NF ‐κB / iNOS system from the inactive “healthy” state into the inflammatory (activated) condi‐ tion is still to be clarified. However, the involve‐ ment of Cav‐1 in the regulation of eNOS / iNOS activation states seems to play a relevant role in vascular inflammation. Compelling evidence shows that caveolae (which are 50–100 nm vesicular invaginations of the endothelial cell membrane) play a cru‐ cial role in vesicular trafficking and modula‐ tion of signal transduction including eNOS reg‐ ulation.5,6 This occurs via Cav‐1, a 21‐to‐24‐kDa The recent study by Mierke et al,1 published in Kardiologia Polska (Kardiol Pol, Polish Heart Journal), highlights the role of caveolin 1 (Cav‐1) / constitutive endothelial nitric oxide synthase (eNOS) in adventitial inflammation and, subse‐ quently, in the progression of vascular smooth muscle cell (VSMC) proliferation. This was as‐ sessed in a model of the denuded aorta from C57Bl6n (wild ‐type), Cav‐1‐/‐, eNOS‐/‐, as well as Cav‐1‐/‐ and eNOS‐/‐ (C/e–/–) mice transplanted into common carotid arteries of wild ‐type mice. This confirms previous background data which showed that the Cav‐1 / eNOS system plays a pro‐ tective role against VSMC proliferation, which is associated with several disease states, includ‐ ing diabetes, hyperlipemia, arterial hyperten‐ sion, etc, leading to atherosclerotic plaque pro‐ gression and atherothrombosis.2 The activity of Cav‐1 / eNOS protective mechanisms is at‐ tenuated by inflammatory stimuli associated with an overproduction of inflammatory cyto‐ kines which, in turn, reduce eNOS release and, via activation of inducible NOS (iNOS) and cy‐ clooxygenase 2, generate large quantities of NO and prostanoids.3 This effect, alongside oxida‐ tive stress, leads to apoptotic cell death of en‐ dothelial cells and VSMC proliferation, though the mechanisms still remains to be elucidated. Evidence clearly showed that a continuous cross ‐modulation exists between eNOS and iNOS under basal conditions as well as in the de‐ velopment of vascular inflammation. Moreover, it is known that eNOS contributes, under basal Correspondence to: Prof. Vincenzo Mollace, MD, PhD, Campus Universitario di Germaneto, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy, email: mollace@unicz.it Received: January 24, 2020. Accepted: January 25, 2020. Published online: February 25, 2020. Kardiol Pol. 2020; 78 (2): 96-97 doi:10.33963/KP.15203 Copyright by the Author(s), 2020 E D I T O R I A L

kardiologia polska

The essential role of a “healthy” relationship between caveolin-1 and endothelial nitric oxide synthase in counteracting vascular inflammation and atherothrombosis