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Published on: February 11, 2017
3D imaging and morphometry of the heart capillary system in spontaneously hypertensive rats and normotensive controls
Camilla Olianti1, Irene Costantini1,2, Francesco Giardini1
1European Laboratory for Non-Linear Spectroscopy, Florence, Italy.
Insights
Hypertension remodels heart capillaries early, increasing density and dispersion before high blood pressure. This vascular change correlates with cellular disarray, offering insights into cardiac pathology.
Area of Science:
- Cardiovascular Biology
- Medical Imaging
- Pathology
Background:
- Systemic arterial hypertension is a prevalent chronic disease linked to hypertensive cardiomyopathy.
- Intramural small coronary artery and arteriole remodeling is a key feature of this condition.
- The implications of this vascular remodeling at the capillary level remain incompletely understood.
Purpose of the Study:
- To investigate the downstream vascular organization at the capillary level in response to hypertensive cardiomyopathy.
- To analyze capillary network remodeling in Spontaneously Hypertensive Rats (SHR) as a model for human hypertensive cardiomyopathy.
- To assess changes in capillary diameter, linear density, and angular dispersion over time.
Main Methods:
- Utilized Spontaneously Hypertensive Rats (SHR) exhibiting features of human hypertensive cardiomyopathy.
- Generated 3D high-resolution mesoscopic reconstructions of the entire coronary vascular network.
- Employed gel-based fluorescent labeling and CLARITY-based tissue clearing for detailed imaging.
- Performed morphometric quantification of the capillary network.
Main Results:
- SHR hearts showed significant capillary network remodeling, with increased capillary density in both ventricles at all ages, even before systemic hypertension onset.
- Capillary angular dispersion increased with time in SHR, correlating strongly with vascular dispersion and cellular disarray.
- These findings suggest capillary remodeling occurs independently of systemic hypertension and left ventricular hypertrophy onset.
Conclusions:
- 3D high-resolution reconstruction of the capillary network is a reliable method for integrated quantitative analyses in cardiac conditions.
- Anatomic signatures of capillary network remodeling can be unveiled in both physiological and pathological cardiac states.
- Early capillary network changes precede overt hypertension, highlighting a potential new avenue for understanding cardiac pathology progression.
Abstract:
Systemic arterial hypertension is a highly prevalent chronic disease associated with hypertensive cardiomyopathy. One important feature of this condition is remodelling of intramural small coronary arteries and arterioles. Here, we investigated the implications of this remodelling in the downstream vascular organization, in particular at the capillary level. We used Spontaneously Hypertensive Rats (SHR) exhibiting many features of the human hypertensive cardiomyopathy. We generated 3D high-resolution mesoscopic reconstructions of the entire network of SHR hearts combining gel-based fluorescent labelling of coronaries with a CLARITY-based tissue clearing protocol. We performed morphometric quantification of the capillary network over time to assess capillary diameter, linear density, and angular dispersion. In SHRs, we found significant remodelling of the capillary network density and dispersion. SHR capillary density is increased in both ventricles and at all ages, including before the onset of systemic hypertension. This result suggests that remodelling occurs independently from the onset of systemic hypertension and left ventricular hypertrophy. On the contrary, capillary angular dispersion increases with time in SHR. Consistently, our multicolor imaging underlined a strong correlation between vascular dispersion and cellular disarray. Together our data show that 3D high-resolution reconstruction of the capillary network can unveil anatomic signatures in both physiological and pathological cardiac conditions, thus offering a reliable method for integrated quantitative analyses.
