Cross-linking influences the impact of quantitative changes in myocardial collagen on cardiac stiffness and remodelling in hypertension in rats.
OBJECTIVE
To assess whether the variable impact of quantitative changes in myocardial collagen on left ventricular (LV) diastolic myocardial stiffness (myocardial k) and remodelling (increased volume intercept of diastolic pressure-volume relations) in LV hypertrophy (LVH) is associated with alterations in myocardial collagen cross-linking.


METHODS
We evaluated myocardial collagen content (hydroxyproline concentrations [HPRO]) and the degree of myocardial collagen cross-linking (solubility to cyanogen bromide digestion) in 14-15- and 21-22-month-old spontaneously hypertensive rats (SHRs), and in aortic-banded rats with pressure overload hypertrophy (POH).


RESULTS
In rats with POH and in SHRs irrespective of age, increases in myocardial [HPRO] were noted. However, hypertensive rats differed in the material and geometric properties of the myocardium, and in qualitative aspects of fibrosis. In 14-15-month-old SHRs myocardial k (determined from diastolic stress-strain relations) and insoluble (cross-linked) [HPRO] were increased, but no LV remodelling or increases in myocardial soluble (non-cross-linked) [HPRO] were noted. In rats with POH, LV remodelling and increases in soluble myocardial [HPRO] occurred, but no increase in k or insoluble myocardial [HPRO] were observed. In 21-22-month-old SHRs, increases in k, soluble and insoluble myocardial [HPRO], as well as LV remodelling occurred.


CONCLUSIONS
Collagen cross-linking may determine the diverse relation that exists between increases in myocardial collagen concentrations and either myocardial stiffness or chamber remodelling in hypertension. These findings support the notion that fibrosis contributes to myocardial stiffness as well as LV dilatation in LVH, albeit an effect that is modulated by collagen quality.
Badenhorst
Danelle
D
Cardiovascular Pathophysiology Research Unit, School of Physiology, University of the Witwatersrand, Johannesburg, South Africa.
Maseko
Muzi
M
Tsotetsi
Oupa J
OJ
Naidoo
Alvin
A
Brooksbank
Richard
R
Norton
Gavin R
GR
Woodiwiss
Angela J
AJ
D000818:Animals; D001835:Body Weight; D003094:Collagen / Q000378:metabolism*; D004548:Elasticity; D006352:Heart Ventricles / Q000473:pathology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
D003094:Collagen