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Published on: August 21, 2020
Histological and morphometric analysis of dilated cardiomyopathy with special reference to collagen IV expression
Parul Jain1, Sudheer Arava1, Sandeep Seth2
1Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Insights
Dilated cardiomyopathy shows non-specific histomorphological changes. Histological parameters do not predict disease progression, as they lack correlation with left ventricular ejection fraction (LVEF).
Area of Science:
- Cardiovascular Pathology
- Cardiac Histomorphology
- Extracellular Matrix Research
Background:
- Dilated cardiomyopathy (DCM) is characterized by known alterations in collagen distribution and microvasculature.
- Histomorphological changes, including microvascular and extracellular matrix modifications, are observed in DCM.
Purpose of the Study:
- To investigate the histomorphological features of DCM.
- To quantitatively correlate these features with left ventricular ejection fraction (LVEF).
- To evaluate alterations in collagen IV distribution and microvasculature in DCM.
Main Methods:
- Analysis of 34 DCM endomyocardial biopsies, 7 explanted hearts, and 41 control hearts.
- Histological staining (H&E, Masson trichrome) and immunohistochemistry (CD34, SMA, Collagen IV).
- Morphometric analysis using Image pro plus 7 software, correlated with LVEF.
Main Results:
- DCM exhibits myocyte hypertrophy, nucleomegaly, interstitial fibrosis, myocarditis, and vessel wall changes.
- Significant increase in nuclear area, myocyte width, and fibrosis percentage; reduced capillary-myocyte ratio.
- Marked alteration in Collagen IV distribution with reduced staining intensity around myocytes.
Conclusions:
- Histomorphological changes in DCM are non-specific.
- Histological parameters do not predict disease progression due to lack of correlation with LVEF.
- Significant alterations in Collagen IV distribution indicate extracellular matrix remodeling in DCM.
Introduction:
Collagen distribution alterations are well known in dilated cardiomyopathy. There are also changes in microvasculature along with other histomorphorphological features.
Aims And Objectives:
To study the histomorphological features of DCM along with their quantitative correlation with LVEF. Alterations in collagen IV distribution pattern and microvasculature in DCM were also evaluated.
Materials And Methods:
The present study includes 34 right ventricular endomyocardial biopsies, 7 explanted native hearts and 41 autopsy control hearts. Sections were taken from lower half of right interventricular septum and stained for H and E, Masson trichrome and immunohistochemistry for CD34, SMA and Collagen IV to study the histological features, pattern of fibrosis, capillary and arteriolar distribution and collagen IV expression respectively. Morphometric analysis was carried out in all cases and controls using Image analysis software Image pro plus 7 and correlated with left ventricular ejection fraction.
Results:
The histomorphological changes of DCM include myocyte hypertrophy, nucleomegaly, and interstitial fibrosis. Interfiber fibrosis was the commonest. There was evidence of myocarditis, ischemic change and vessel wall alterations. Considerable alteration in Collagen IV distribution was observed with reduction in intensity and proportion of staining around myocytes quantified using Allred scoring against uniform pericellular staining in controls. Morphometric analysis revealed significant increase in nuclear area, myocyte width, percentage of fibrosis and reduction in capillary myocyte ratio in cases as compared to controls. There was no significant difference in arteriolar density. No significant association was observed between morphometric parameters and LVEF.
Conclusion:
Histomorphological changes in DCM are non-specific. Quantitation of histological parameters cannot be used to predict the disease progression as there was no significant correlation with LVEF. There is appreciable alteration in Collagen IV distribution in DCM owing to extracellular matrix alterations.
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