Angiotensin-converting enzyme inhibitors modulate the activation of the tissue factor pathway within aortic valves in patients with aortic stenosis: Links between blood coagulation and inflammation

Abstract

Background: Similarities between the pathobiology of aortic stenosis (AS) and atherosclerosis have led to the concept that pharmacological strategies effective in atherosclerosis might attenuate valvular inflammation. Objective: The objective of this study was to assess how angiotensin-converting enzyme inhibitors (ACEIs) might affect valvular expression of coagulation and inflammatory proteins in AS. Material/Methods: We studied 111 advanced AS patients (62 males, aged 63.3±11.2 years) undergoing valve replacement. Plasma levels, valvular expression and mRNA transcripts of tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, along with C-reactive protein (CRP) and interleukin-6 (IL-6) were evaluated. Results: TF-, TFPI-, CRP and prothrombin valvular expression was not related to demographics, concomitant diseases or plasma TF, free-TFPI or IL-6. ACEIs-treated patients (n=37), mainly due to hypertension (n=24, 65%), showed decreased areas for valvular TF (13.64±6.43 vs. 18.05±6.81%, p=0.03), TFPI (32.6±7.8 vs. 49.15±9.5%, p<0.001), prothrombin (23.47±1.93 vs. 26.61±1.4%, p<0.001), CRP (0.75 [0-9] vs. 1.4 [0-8]%, p=0.009), and IL-6 (3.2±0.65 vs. 6.4±1.83%, p<0.001) compared with non-ACEIs patients. Similarly, patients treated with ACEIs showed lower mRNA expression of TF (1.22±0.47 vs. 2.27±1.42, p=0.041), prothrombin (0.13±0.07 vs. 0.81±0.37, p<0.001), CRP (0.73±0.29 vs. 1.25±0.69, p=0.04), and IL-6 (7.6±5.16 vs. 13.67±7.3, p=0.046). Conclusions: In patients with severe AS, ACEIs use is associated with lower expression of valvular proteins involved in coagulation and inflammation, thus ACEIs therapy could be important in altering atherosclerosis-like processes within stenotic aortic valves.