3D imaging and morphometry of the heart capillary system in spontaneously hypertensive rats and normotensive controls

Year: 2020

Authors: Olianti C., Costantini I., Giardini F., Lazzeri E., Crocini C., Ferrantini C., Pavone FS., Camici PG., Sacconi L.

Autors Affiliation: European Lab Nonlinear Spect, Florence, Italy; CNR, Natl Inst Opt, Florence, Italy;‎ Univ Colorado, Boulder, CO 80309 USA; Univ Florence, Florence, Italy;‎ Univ Vita Salute San Raffaele, Milan, Italy;‎ Univ Freiburg, Inst Expt Cardiovasc Med, Freiburg, Germany

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.


Volume: 10 (1)      Pages from: 14276-1  to: 14276-9

More Information: This work was supported by the European Union Horizon 2020 research and innovation program under Grant Agreement [654148: Laserlab-Europe]; by the Italian Ministry for Education, University and Research in the framework of the Flagship Project [NANOMAX]; by Ente Cassa Risparmio di Firenze [WHOLE-HEART]; and by FAS-Salute [ToRSADE Project]. C.C was supported by Human Frontiers Science Program fellowship (LT001449/2017-L) and by the American Heart Association (AHA) postdoctoral fellowship (20POST35211113).
KeyWords: Systemic arterial hypertension, clearing, heart, vessels, capillary network, SHR
DOI: 10.1038/s41598-020-71174-9

Citations: 15
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