Myofibroblasts in the cirrhotic rat liver reflect hepatic remodeling and correlate with fibrosis and sinusoidal capillarization

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Abstract

Background/Aims:

Myofibroblasts are essential in fibrogenesis during development of cirrhosis. In the present study we stereologically quantitated MFB's and correlated them with fibrosis and sinusoidal capillarization.

Methods:

Male SD rats were rendered cirrhotic by chronic exposure to phenobarbital/CCl4, (CIR; n=16); untreated littermates served as controls (CTR; n=10). Sinusoidal capillarization was assessed by a multiple indicator dilution technique as previously described. The volume fractions of myofibroblasts and other liver components were estimated by morphometry.

Results:

Myofibroblasts averaged 15.7±SD 0.7% in CIR as compared to 6.7%±SD 0.4% in CTR (p<0.01). An extra-littoral compartment of myofibroblasts was found in portal tracts and within fibrous septa. In CIR, hepatocytes showed a bimodal distribution of volume fractions, and hepatocyte volume distribution disclosed a mirror image of that of myofibroblasts. Connective tissue was markedly increased in CIR, averaging 13.2±1.2% in CIR vs. 1.2±0.3% in CTR (p<0.0001). Extravascular albumin space - a measure of sinusoidal capillarization - was reduced by 44% in CIR (0.028±0.017 vs. 0.050±0.010 ml/g; p<0.001). The volume fraction of myofibroblasts correlated best with extravascular albumin space (r=−0.84, p<0.001). Multiple regression analysis selected only extravascular albumin space and connective tissue to be determined by the volume fraction of myofibroblasts (r=0.923; p<0.001).

Conclusion:

We conclude that increased myofibroblasts reflect the degree of hepatic remodeling rather than cirrhosis inasmuch as myofibroblast volume fraction inversely reflects that of hepatocyte bimodality. Myofibroblasts form an extralittoral compartment in this model of CIR and correlate with hepatic fibrosis and sinusoidal capillarization.

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