4 research outputs found
Remodelado miocárdico en la insuficiencia cardiaca con fracción de eyección preservada en la rata Dahl/SS
El miocardio de las ratas Dahl/SS con ICFEP presenta las alteraciones propias del remodelado miocárdico en la ICFEP: fibrosis miocárdica, hipertrofia de los CMs y rarefacción de los capilares intramiocárdicos. Estos aspectos se asocian con el desarrollo de HVI y DD, haciendo de este modelo una herramienta adecuada para estudiar la ICFEP humana. La fibrosis miocárdica de las ratas Dahl/SS con ICFEP se caracteriza por un aumento del depósito de las fibras de colágeno tanto en la zona perivascular como en el espacio intersticial. Este incremento no se limita al VI sino que afecta también al VD y al SI
Cardiotrophin-1 in hypertensive heart disease
Hypertensive heart disease, here defined by the presence of pathologic left ventricular hypertrophy in the absence of a cause other than arterial hypertension, is characterized by complex changes in myocardial structure including enhanced cardiomyocyte growth and non-cardiomyocyte alterations that induce the remodeling of the myocardium, and ultimately, deteriorate left ventricular function and facilitate the development of heart failure. It is now accepted that a number of pathological processes mediated by mechanical, neurohormonal, and cytokine routes acting on the cardiomyocyte and the non-cardiomyocyte compartments are responsible for myocardial remodeling in the context of arterial hypertension. For instance, cardiotrophin-1 is a cytokine member of the interleukin-6 superfamily, produced by cardiomyocytes and non-cardiomyocytes in situations of biomechanical stress that once secreted interacts with its receptor, the heterodimer formed by gp130 and gp90 (also known as leukemia inhibitory factor receptor beta), activating different signaling pathways leading to cardiomyocyte hypertrophy, as well as myocardial fibrosis. Beyond its potential mechanistic contribution to the development of hypertensive heart disease, cardiotrophin-1 offers the opportunity for a new translational approach to this condition. In fact, recent evidence suggests that cardiotrophin-1 may serve as both a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients, and a potential target for therapies aimed to prevent and treat hypertensive heart disease beyond blood pressure control
Cardiotrophin-1 in hypertensive heart disease
Hypertensive heart disease, here defined by the presence of pathologic left ventricular hypertrophy in the absence of a cause other than arterial hypertension, is characterized by complex changes in myocardial structure including enhanced cardiomyocyte growth and non-cardiomyocyte alterations that induce the remodeling of the myocardium, and ultimately, deteriorate left ventricular function and facilitate the development of heart failure. It is now accepted that a number of pathological processes mediated by mechanical, neurohormonal, and cytokine routes acting on the cardiomyocyte and the non-cardiomyocyte compartments are responsible for myocardial remodeling in the context of arterial hypertension. For instance, cardiotrophin-1 is a cytokine member of the interleukin-6 superfamily, produced by cardiomyocytes and non-cardiomyocytes in situations of biomechanical stress that once secreted interacts with its receptor, the heterodimer formed by gp130 and gp90 (also known as leukemia inhibitory factor receptor beta), activating different signaling pathways leading to cardiomyocyte hypertrophy, as well as myocardial fibrosis. Beyond its potential mechanistic contribution to the development of hypertensive heart disease, cardiotrophin-1 offers the opportunity for a new translational approach to this condition. In fact, recent evidence suggests that cardiotrophin-1 may serve as both a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients, and a potential target for therapies aimed to prevent and treat hypertensive heart disease beyond blood pressure control
Association of cystatin C with heart failure with preserved ejection fraction in elderly hypertensive patients: potential role of altered collagen metabolism
Objectives: Cystatin C has been shown to be associated
with heart failure with preserved ejection fraction (HFPEF).
In addition, myocardial fibrosis has been involved in
diastolic dysfunction in HFPEF. Therefore, we hypothesized
that increased cystatin C levels may be associated with
altered collagen metabolism, contributing to diastolic
dysfunction in patients with HFPEF.
Methods: One hundred and forty-one elderly hypertensive
patients with HFPEF were included. Cardiac morphology
and function was assessed by echocardiography.
Circulating levels of cystatin C, biomarkers of collagen type
I synthesis (carboxy-terminal propeptide of procollagen
type I) and degradation [matrix metalloproteinase-1 (MMP-
1) and its inhibitor TIMP-1] and osteopontin were analyzed
by ELISA. Twenty elderly sex-matched patients with no
identifiable cardiac disease were used as controls. In-vitro
studies were performed in human cardiac fibroblasts.
Results: Compared with controls, cystatin C was increased
(P < 0.001) in patients with HFPEF, even in those with a
normal estimated glomerular filtration rate (eGFR;
P < 0.05). Cystatin C was directly correlated with the
estimated pulmonary capillary wedge pressure (P < 0.01),
TIMP-1 and osteopontin (P < 0.001) and inversely
correlated with MMP-1:TIMP-1 (P < 0.01), but not with
carboxy-terminal propeptide of procollagen type I or MMP-
1 in all patients with HFPEF. These associations were
independent of eGFR. In vitro, osteopontin (P < 0.01) and
TIMP-1 (P < 0.001) increased in the supernatant of cardiac
fibroblasts exposed to cystatin C.
Conclusion: In patients with HFPEF of hypertensive origin,
cystatin C is increased and associated with diastolic
dysfunction and alterations in collagen metabolism
independently of eGFR. An excess of cystatin C might
contribute to diastolic dysfunction in HFPEF by facilitating
myocardial fibrosis via accumulation of osteopontin and
TIMP-1