Serum Osteoprotegerin and Carotid Intima-Media Thickness Are Related to High Arterial Stiffness in Heart Failure with Reduced Ejection Fraction

Fehérvári, Lajos; Frigy, Attila; Kocsis, Lóránd; Szabó, István Adorján; Szabo, Timea Magdolna; Urkon, Melinda; Jakó, Zita; Nagy, E

doi:10.3390/diagnostics11050764

Cited by 7 publications

(7 citation statements)

References 58 publications

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“…Dkk‐1 is an important regulator in the Wnt signalling pathway and is involved in bone remodelling processes, 55 rheumatic diseases, and cancer. 56 It could be shown that Dkk‐1 correlates with arterial stiffness, 57 which in turn is an important factor in the pathophysiology of HFpEF. 58 Otherwise, Dkk‐1 could be a new target for further research on biomarkers or therapeutic intervention, like an inhibition by monoclonal antibodies.…”

Section: Discussionmentioning

confidence: 99%

Biomarker profiles in heart failure with preserved vs. reduced ejection fraction: results from the DIAST‐CHF study

et al. 2022

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Aims Chronic heart failure (HF) is a common disease and one of the leading causes of death worldwide. Heart failure with preserved ejection fraction (HFpEF) and with reduced ejection fraction (HFrEF) are different diseases with distinct as well as comparable pathophysiologies and diverse responses to therapeutic agents. We aimed to identify possible pathobiochemical signalling pathways and biomarkers in HFpEF and HFrEF by using a broad proteomic approach. Methods and results A total of 180 biomarkers in the plasma of a representative subgroup (71 years old) of HFpEF (70% female) with a left ventricular ejection fraction (LVEF) ≥ 50% and HFrEF (18% female) with an LVEF ≤ 40% patients ( n = 127) from the Prevalence and Clinical Course of Diastolic Dysfunction and Diastolic Heart Failure (DIAST‐CHF) trial were examined and compared with a healthy control group ( n = 40; 48% female). We were able to identify 35 proteins that were expressed significantly different in both HF groups compared with the control group. We determine 29 unique proteins expressed in HFpEF and 33 unique proteins in HFrEF. Significantly up‐regulated trefoil factor 3 (TFF3) and down‐regulated contactin‐1 could be identified as previously unknown biomarkers for HF. However, TFF3 is also a predictive factor for the occurrence of a cardiovascular event in HFpEF patients. In HFpEF, serine protease 27 was found at reduced levels for the first time, which could offer a new therapeutic target. Additionally, network analyses showed a special role of platelet‐derived growth factor subunit A, Dickkopf‐related protein 1, and tumour necrosis factor receptor superfamily member 6 in HFpEF patients, whereas perlecan and junctional adhesion molecule A stood out in the HFrEF group. Overall, signalling pathways of metabolic processes, cellular stress, and iron metabolism seemed to be important for HFrEF, whereas for HFpEF, oxygen stress, haemostasis, cell renewal, cell migration, and cell proliferation are in the foreground. Conclusions The identified proteins and signalling pathways offer new therapeutic and diagnostic approaches for patients with chronic HF.

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Section: Discussionmentioning

confidence: 99%

Biomarker profiles in heart failure with preserved vs. reduced ejection fraction: results from the DIAST‐CHF study

et al. 2022

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“…Multiple studies have demonstrated a significant association between serum sclerostin concentration and higher arterial stiffness (Table 3). 48,[60][61][62][63][64] In contrast, Thambiah et al 68 reported no significant association between serum sclerostin concentration and pulse wave velocity in patients with CKD. One explanation for the disparate findings could be that the latter study included patients with mild CKD since none had ESRF.…”

Section: Human Blood Samplesmentioning

confidence: 99%

“…Fourteen studies examining the association between serum sclerostin concentration and arterial stiffness or atherosclerosis severity were identified. 48,[56][57][58][59][60][61][62][63][64][65][66][67][68] Twelve studies reported significant positive associations, 48,[56][57][58][59][60][61][62][63][64][65][66] while one study reported a negative association 67 and one study reported no association. 68 Higher serum sclerostin has been associated with coronary, carotid, and peripheral atherosclerosis.…”

Section: Human Blood Samplesmentioning

confidence: 99%

Role of Sclerostin in Cardiovascular Disease

Golledge

Thanigaimani

2022

ATVB

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Sclerostin is most recognized for its role in controlling bone formation but is also expressed in the heart, aorta, coronary, and peripheral arteries. This review summarizes research on sclerostin’s role in cardiovascular disease. Rodent studies have found sclerostin to be expressed at sites of arterial calcification. In contrast, aortic sclerostin was reported to be downregulated in a mouse model of abdominal aortic aneurysm, and transgenic upregulation or administration of sclerostin was found to prevent abdominal aortic aneurysm and atherosclerosis formation. Sclerostin deficiency was reported to stimulate cardiac rupture in one rodent model. In humans, 7 of 11 studies reported a significant association between high serum sclerostin and high carotid intima media thickness. Ten of 15 studies reported a significant association between high serum sclerostin and severe arterial calcification. Twelve of 14 studies reported a significant association between high serum sclerostin and high arterial stiffness or atherosclerosis severity. Four of 9 studies reported a significant association between high serum sclerostin and high risk of cardiovascular events. A meta-analysis of randomized controlled trials suggested that administration of the sclerostin blocking antibody romosozumab did not significantly increase the risk of major adverse cardiovascular events (risk ratio, 1.14 [95% CI, 0.83–1.57]; P =0.54) or cardiovascular death (risk ratio, 0.92 [95% CI, 0.53–1.59]; P =0.71). Human genetic studies reported variants predisposing to low arterial sclerostin expression were associated with a high risk of cardiovascular events. Overall, past research suggests a cardiovascular protective role of sclerostin but findings have been inconsistent, possibly due to variations in study design, the unique populations and models studied, and the heterogeneous methods used.

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“…However, some observations reporting the elevation of TNF-α, IL-1β, and IL-6 have a limited sample size or lack proper adjustment. Some studies found increased concentrations of TNF receptors (TNFR1 and TNFR2) or elevated levels of molecules pertaining to the TNF receptor superfamily, like Fas or osteoprotegerin (OPG) [ 10 , 13 ].…”

Section: Systemic Inflammatory Cytokines Influence Intracellular Calcium Homeostasis and Myocardial Contractilitymentioning

confidence: 99%

Targeting Mediators of Inflammation in Heart Failure: A Short Synthesis of Experimental and Clinical Results

Szabo

Frigy

Nagy

2021

IJMS

Self Cite

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Inflammation has emerged as an important contributor to heart failure (HF) development and progression. Current research data highlight the diversity of immune cells, proteins, and signaling pathways involved in the pathogenesis and perpetuation of heart failure. Chronic inflammation is a major cardiovascular risk factor. Proinflammatory signaling molecules in HF initiate vicious cycles altering mitochondrial function and perturbing calcium homeostasis, therefore affecting myocardial contractility. Specific anti-inflammatory treatment represents a novel approach to prevent and slow HF progression. This review provides an update on the putative roles of inflammatory mediators involved in heart failure (tumor necrosis factor-alpha; interleukin 1, 6, 17, 18, 33) and currently available biological and non-biological therapy options targeting the aforementioned mediators and signaling pathways. We also highlight new treatment approaches based on the latest clinical and experimental research.

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Serum Osteoprotegerin and Carotid Intima-Media Thickness Are Related to High Arterial Stiffness in Heart Failure with Reduced Ejection Fraction

Cited by 7 publications

References 58 publications

Biomarker profiles in heart failure with preserved vs. reduced ejection fraction: results from the DIAST‐CHF study

Biomarker profiles in heart failure with preserved vs. reduced ejection fraction: results from the DIAST‐CHF study

Role of Sclerostin in Cardiovascular Disease

Targeting Mediators of Inflammation in Heart Failure: A Short Synthesis of Experimental and Clinical Results

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