The Role of Matrix Metalloproteinases 2 and 9 in Vascular and Ventricular Remodelling in Patients with Heart Failure with Preserved Ejection Fraction

Abstract

Imbalance of activation and inhibition of matrix metalloproteinases (MMPs) lead to an increase in their activity and the occurrence of pathological changes in the vascular wall. The purpose of this paper is to determine the role of MMP-2 and MMP-9 in vascular and ventricular remodelling in patients with heart failure with preserved ejection fraction. The patients were divided into three groups: 15 patients with heart failure with preserved ejection fraction (HFpEF), 72.73 ± 10.44 years old; 15 patients with arterial hypertension (AH), 63.73 ± 7.06 years old; 10 healthy controls, 58.7 ± 5.87 years old. Arterial stiffness was assessed by pulse wave velocity (PWV). Diastolic dysfunction was assessed by the ratio of early diastolic mitral flow velocity and early diastolic myocardial velocity (E/Em ratio). Left ventricular mass was calculated by area-length method and indexed to body surface area (LVMI). MMP-2, MMP-9 and Brain Natriuretic Peptide (BNP) were measured by ELISA technique.MMP-2 was higher in patients with HFpEF and AH versus controls (13987 ± 4464 ng/ml and 13040 ± 5060 ng/ml vs 9260 ± 4135 ng/ml, p = 0.047). MMP-9 was similar across the groups. BNP was higher in HFpEF versus AH and controls (775.33±443.59 pg/ml vs 370.00±158.29 pg/ml and 345.00±94.39 pg/ml, p = 0.002). In HFpEF patients, PWV (12.04 ± 2.46 m/s vs 10.06 ± 1.94 m/s vs 7.22±1.19 m/s, p < 0.0001), LVMI (134.11±29.40 g/m 2 vs 122.45±23.73Elisa kits for MMP-2, MMP-9 and BNP were purchased with funds from project "Young researcher" No 4D/2011 of the Medical University of Sofia. 289 g/m 2 vs 101.66 ± 11.92 g/m 2 , p < 0.0001), E/Em (16.30 ± 6.80 vs 9.57 ± 2.70 and 8.15 ± 1.63, p < 0.0001) were significantly higher, compared to hypertensive patients and controls. Higher MMP-2 was associated with higher PWV (r = 0.43, p = 0.007), E/Em (r = 0.40, p = 0.011) and LVMI (r = 0.46, p = 0.003). The measuring of MMP-2 could be useful for early detection of high risk patients and initiation of therapy before the development of organ damage.

Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction

“…The current study demonstrates a 14% reduction in BV in stable HFpEF patients compared with control individuals. In absolute terms, BV levels in HFpEF patients were slightly lower compared with those of stable HFrEF patients reported in other studies (Abramov et al , #61; Miller , #64) As expected, HFpEF patients also presented with increased stiffness of central elastic arteries as determined by augmented carotid–femoral PWV, previously attributed, among other factors, to the exacerbated degradation of elastic fibers in the arterial wall mediated by proteolytic enzymes such as matrix metalloproteinase‐2 and ‐9 (Yasmin et al ; Somleva et al ). With regard to compounding effects of hypovolemia and arterial stiffness, experimental studies indicate that decreased BV impairs ventricular filling, stroke volume, and cardiac output specifically in the HFpEF phenotype, notably in the presence of exacerbated stiffening of the cardiovascular system (Nagano et al ).…”

Heart failure in patients with high homocysteine levels

“…40 In particular, MMP-2 was found significantly high in HfpEF-patients before the occurrence of symptoms, even if its pathogenic role is unknown. 41 Finally, referring to the relationship between HHcy and HfpEF%, the Framingham Heart Study reports that plasma HHcy is directly related to left ventricular mass and wall thickness. 42 A previous study of Cesari et al confirmed a strong association between HHcy and HfpEF%.…”