Decreased immunoreactivity of von Willebrand factor may reflect persistent nature of the endothelial dysfunction in non-ischemic heart failure
Abstract
Introduction. Endothelial dysfunction is a critical part of heart failure (HF) pathophysiology. It is not clear, however, whether it is present at the similar level in the early and late HF stages.
Material and methods. von Willebrand factor (vWF) and its mRNA levels in biopsies of non-ischemic patients with HF secondary to dilated cardiomyopathy were studied. Consecutive patients with HF were divided into two groups: group A with disease duration ≤ 12 months (n = 59) and group B with disease duration > 12 months (n = 68). The immunoreactivity of the vWF was compared with autopsy sections of 19 control cases. Tissue vWF gene expression was analyzed at the mRNA level by RT-PCR.
Results. In the group A, there was lower vWF immunoreactivity in the coronary microvessels compared to the group B [1.5 (1.0–2.0) vs. 2.0 (1.5–2.4), P = 0.001]. In the control group, only weak vWF expression was observed. Protein expression was not accompanied by vWF mRNA whose levels were significantly higher in the Group A as compared to the Group B [14671 (4932-51561) vs. 3643 (185.3–9030.8), P = 0.005]. Protein vWF expression was inversely associated with its mRNA levels (r = –0.34, P = 0.04).
Conclusions. High myocardial protein expression of vWF in patients with long-lasting HF symptoms may
highlight the persistent nature of endothelial dysfunction in such a cohort of patients.
Keywords: heart failuredilated cardiomyopathyendomyocardial biopsyendothelial dysfunctionvon Willebrand factorqPCRIHC
References
- Rosamond W, Flegal K, Furie K, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008; 117(4): e25–146.
- Mosterd A, Hoes AW, Mosterd A, et al. Clinical epidemiology of heart failure. Heart 2007;93:1137-1146. .
- Inoue T, Sakai Y, Morooka S, et al. Coronary flow reserve in patients with dilated cardiomyopathy. Am Heart J. 1993; 125(1): 93–98.
- Salgado DR, Favory R, Rocco JR, et al. Microcirculatory effects of angiotensin II inhibitors in patients with severe heart failure. Clin Hemorheol Microcirc. 2013; 54(1): 87–98.
- van Hinsbergh VWM. Endothelium--role in regulation of coagulation and inflammation. Semin Immunopathol. 2012; 34(1): 93–106.
- Zuchi C, Tritto I, Carluccio E, et al. Role of endothelial dysfunction in heart failure. Heart Fail Rev. 2020; 25(1): 21–30.
- Chen JW, Ting CT, Chen YH, et al. Differential coronary microvascular function in patients with left ventricular dysfunction of unknown cause — implication for possible mechanism of myocardial ischemia in early stage of cardiomyopathy. Int J Cardiol. 1999; 69(3): 251–261.
- Heuvel Av, Veldhuisen Dv, Wall Ev, et al. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2000; 35(1): 19–28.
- Neglia D, Michelassi C, Trivieri MG, et al. Prognostic role of myocardial blood flow impairment in idiopathic left ventricular dysfunction. Circulation. 2002; 105(2): 186–193.
- Fischer D, Rossa S, Landmesser U, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J. 2005; 26(1): 65–69.
- Katz SD, Hryniewicz K, Hriljac I, et al. Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation. 2005; 111(3): 310–314.
- Lerman A, Zeiher A. Endothelial Function. Circulation. 2005; 111(3): 363–368.
- Ruggeri Z. Structure and Function of von Willebrand Factor. Thromb Haemost. 2017; 82(08): 576–584.
- Gombos T, Makó V, Cervenak L, et al. Levels of von Willebrand factor antigen and von Willebrand factor cleaving protease (ADAMTS13) activity predict clinical events in chronic heart failure. Thromb Haemost. 2009; 102(3): 573–580.
- Nowroozpoor A, Gutterman D, Safdar B. Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? - A scoping review. Microvasc Res. 2021; 134: 104123.
- Galatius S, Wroblewski H, Sørensen V, et al. Endothelin and von Willebrand factor as parameters of endothelial function in idiopathic dilated cardiomyopathy: Different stimuli for release before and after heart transplantation? Am Heart J. 1999; 137(3): 549–554.
- El-Mansi S, Nightingale TD. Emerging mechanisms to modulate VWF release from endothelial cells. Int J Biochem Cell Biol. 2021; 131: 105900.
- Kleber ME, Koller L, Goliasch G, et al. Von Willebrand factor improves risk prediction in addition to N-terminal pro-B-type natriuretic peptide in patients referred to coronary angiography and signs and symptoms of heart failure and preserved ejection fraction. Circ Heart Fail. 2015; 8(1): 25–32.
- Zannad F, Stough WG, Regnault V, et al. Is thrombosis a contributor to heart failure pathophysiology? Possible mechanisms, therapeutic opportunities, and clinical investigation challenges. Int J Cardiol. 2013; 167(5): 1772–1782.
- Lip GYH, Pearce LA, Chin BSP, et al. Effects of congestive heart failure on plasma von Willebrand factor and soluble P-selectin concentrations in patients with non-valvar atrial fibrillation. Heart. 2005; 91(6): 759–763.
- Gibbs CR, Blann AD, Watson RD, et al. Abnormalities of hemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm: effects of angiotensin-converting enzyme inhibitor and beta-blocker therapy. Circulation. 2001; 103(13): 1746–1751.
- Fukuchi M, Watanabe J, Kumagai K, et al. Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage. J Am Coll Cardiol. 2001; 37(5): 1436–1442.