Protein synthesis in the hypertrophied heart of spontaneously hypertensive rats and a comparison of the effects of an ACE-inhibitor and a calcium channel antagonist

1995 ◽  
Vol 13 (2) ◽  
pp. 111-124 ◽  
Author(s):  
V. B. Patel ◽  
T. Siddiq ◽  
P. J. Richardson ◽  
V. R. Preedy
Keyword(s):  
Protein Synthesis ◽  
Calcium Channel ◽  
Calcium Channel Antagonist ◽  
Spontaneously Hypertensive Rats ◽  
Ace Inhibitor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Hypertrophied Heart

scholarly journals Transient ACE (Angiotensin-Converting Enzyme) Inhibition Suppresses Future Fibrogenic Capacity and Heterogeneity of Cardiac Fibroblast Subpopulations

Hypertension ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 904-918
Author(s):  
Alexandra M. Garvin ◽  
Matthew D. De Both ◽  
Joshua S. Talboom ◽  
Merry L. Lindsey ◽  
Matthew J. Huentelman ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Ace Inhibitor ◽  
Ace Inhibition ◽  
Cardiac Fibroblast ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Single Cell Rna Sequencing ◽  
Converting Enzyme Inhibition

Transient ACE (angiotensin-converting enzyme) inhibition in spontaneously hypertensive rats is known to protect against future injury-induced cardiac inflammation, fibrosis, and dysfunction; however, the mechanisms of protection have not been delineated. Here, we used single-cell RNA sequencing to test the hypothesis that transient ACE inhibitor treatment would induce a persistent shift in cardiac fibroblast subpopulations. Adult male spontaneously hypertensive rats (11 weeks old, hypertensive with cardiac hypertrophy) were treated for 2 weeks with an ACE inhibitor, enalapril (30 mg/kg per day, PO), or water (untreated spontaneously hypertensive rats) followed by a 2-week washout period (n=7/group). Cardiac fibroblasts were isolated from the left ventricle and subjected to single-cell RNA sequencing. Nine clusters of fibroblasts were identified, with 98% of cells in clusters 0 to 6. The transient treatment produced significant changes both within and across clusters. Cluster 1 depicted a highly fibrogenic gene profile, with cluster 6 serving as a gateway to cluster 1. Transient ACE inhibition depleted the gateway and expanded cluster 0, which was the least fibrogenic profile. Moreover, within cluster 1 fibroblasts, ACE inhibition reduced expression of individual fibrosis genes (eg, COL1A1, COL3A1 , and FN1 ; all P <1×10 -35 ). Clusters 2 to 5 reflected proliferative, moderately fibrogenic, translationally active, and less inflammatory subsets of fibroblasts, all of which exhibited attenuated fibrogenic gene expression after transient ACE inhibition. In conclusion, transient ACE inhibition shifts cardiac fibroblast subpopulations and degree of activation resulting in an overall reduced fibrogenic phenotype.

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