Cross-linking influences the impact of quantitative changes in myocardial collagen on cardiac stiffness and remodelling in hypertension in rats

Badenhorst, Danelle; Maseko, Muzi J.; Tsotetsi, Oupa J.; Naidoo, Alvin; Brooksbank, Richard; Norton, Gavin R.; Woodiwiss, Angela J.

doi:10.1016/s0008-6363(02)00733-2

Cited by 142 publications

(116 citation statements)

References 24 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…8 Other than variations in intrinsic cardiomyocyte stiffness, 20 changes in the collagen matrix also influence myocardial stiffness. In particular, Badenhorst et al 12 demonstrated in experimental models of pressure overload that myocardial and LV chamber stiffness are affected by changes in both collagen quantity and quality (ie, cross-linking), with the effects of changes in CCL indicates collagen cross-linking; InsCol, insoluble collagen; C I VF, collagen type I volume fraction; CVF, total collagen volume fraction; LOX, lysyl oxidase; PCWP, pulmonary capillary wedge pressure; PFR, peak filling rate; LVEF, left ventricular ejection fraction; NS, nonsignificant.…”

Section: Discussionmentioning

confidence: 99%

“…9 In fact, as demonstrated in different experimental models of pressure overload, although LV chamber stiffness is affected by changes in both collagen quantity and quality, the effects of changes in collagen quantity, particularly the abundance of collagen type I, are modified by collagen quality, in particular the degree of CCL. [10][11][12] Therefore, a more complete understanding of the quantitative and qualitative variations of myocardial collagen matrix and their impact on LV function is critical as we strive to develop specific and effective therapies for HF. In this conceptual framework, this study was designed to investigate whether it is the quantity (as assessed by the amounts of total or collagen type I fibers) or the quality (as assessed by the degree of CCL and availability of insoluble collagen [insCol]) that associates with FPs in hypertensive patients with HHD and chronic stage C HF.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure

et al. 2012

View full text Add to dashboard Cite

Abstract-We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. Key Words: collagen Ⅲ filling pressures Ⅲ heart failure A rterial hypertension has been long considered as one of the most common etiologic conditions predisposing to heart failure (HF).1 Furthermore, a recent systematic review shows that HF development remains a major problem in treated hypertensive patients.2 It has been shown that myocardial fibrosis, a common finding in postmortem studies and endomyocardial biopsies of patients with hypertensive heart disease (HHD), 3 is associated with the increase of left ventricular (LV) chamber stiffness 4,5 and the development of clinically overt HF in these patients. 6,7 It has been proposed that the increase in LV stiffness can contribute to compromised diastolic function and elevate left-sided filling pressures (FPs) in hypertensive patients. 8 The definition of myocardial fibrosis is based on the quantification of an excess of collagen fiber deposition, as assessed by staining techniques. However, it must be considered that collagen-dependent LV chamber stiffness is influenced not only by the amount of collagen fibers but also by their qualitative properties (ie, the degree of collagen crosslinking [CCL] among collagen fibrils that determines the insolubility, stiffness, and resistance to degradation of the resulting fibers; the relative proportions of collagen types I and III fibers; and the diameter of the collagen fibers and their spatial alignment). 9 In fact, as demonstrated in different experimental models of pressure overload, although LV chamber stiffness is affected by changes in both collagen

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Increased ColI deposition in ColVa1ϩ/Ϫ;ColXIa1Ϫ/Ϫ hearts is observed in both the myocardium and valves, although quantitative levels are not significantly different from singlemutant mice. The ratio of ColI to ColIII has been previously shown to be important for determining the mechanical integrity of cardiac tissue (Badenhorst et al, 2003). In general, higher levels of ColI compared with ColIII is associated with tissue stiffness, whereas greater levels of ColIII promote tissue elasticity (Iimoto et al, 1988;Kato et al, 1995;Badenhorst et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…The ratio of ColI to ColIII has been previously shown to be important for determining the mechanical integrity of cardiac tissue (Badenhorst et al, 2003). In general, higher levels of ColI compared with ColIII is associated with tissue stiffness, whereas greater levels of ColIII promote tissue elasticity (Iimoto et al, 1988;Kato et al, 1995;Badenhorst et al, 2003). In this study, the relative immunoreactivity levels of ColI and ColIII were different in the cardiac tissues of ColVa1ϩ/Ϫ, ColXIa1Ϫ/Ϫ and ColVa1ϩ/Ϫ; ColXIa1Ϫ/Ϫ mice, which would lead to altered ratios of ColI to ColIII, depending on the genotype.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have described the importance of ColI to ColIII ratios for mechanical properties of cardiac tissue (Badenhorst et al, 2003). Therefore, the fold change of immunoreactivity for ColIII was measured in the mitral valve leaflet and myocardium of ColVa1ϩ/Ϫ, ColXIa1Ϫ/Ϫ, and ColVa1ϩ/Ϫ;ColXIa1Ϫ/Ϫ mice over wild-type controls.…”

Section: Coliii Immunoreactivity Is Increased In Hearts Frommentioning

confidence: 99%

See 1 more Smart Citation

ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve development

Lincoln

Florer

Deutsch

et al. 2006

Developmental Dynamics

View full text Add to dashboard Cite

Genetic mutations in minor fibrillar collagen types Va1 (ColVa1) and XIa1 (ColXI) have been identified in connective tissue disorders including Ehlers-Danlos syndrome and chondrodysplasias. ColVa1؉/؊ and ColXIa1؊/؊ mutant mice recapitulate these human disorders and show aberrations in collagen fiber organization in connective tissue of the skin, cornea, cartilage, and tendon. In the heart, fibrous networks of collagen fibers form throughout the ventricular myocardium and heart valves, and alterations in collagen fiber homeostasis are apparent in many forms of cardiac disease associated with myocardial dysfunction and valvular insufficiency. There is increasing evidence for cardiac dysfunction in connective tissue disorders, but the mechanisms have not been addressed. ColVa1؉/؊ and ColXIa1؊/؊ mutant mice were used to identify roles for ColVa1 and ColXIa1 in ventricular myocardial morphogenesis and heart valve development. These affected cardiac structures show a compensatory increase in type I collagen deposition, similar to that previously described in valvular and cardiomyopathic disease. Morphological cardiac defects associated with changes in collagen fiber homeostasis identified in ColVa1؉/؊ and ColXIa1؊/؊ mice provide an insight into previously unappreciated forms of cardiac dysfunction associated with connective tissue disorders. Developmental Dynamics 235:3295-3305, 2006.

show abstract

Ventricular Function in Pressure Overload Lesions

Colan¹

2005

Ventricular Function and Blood Flow in Congenital Heart Disease

View full text Add to dashboard Cite

Cross-linking influences the impact of quantitative changes in myocardial collagen on cardiac stiffness and remodelling in hypertension in rats

Cited by 142 publications

References 24 publications

Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure

Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure

ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve development

Ventricular Function in Pressure Overload Lesions

Contact Info

Product

Resources

About