Fibrocytes are Increased in the Medial Layer of the Aorta from Spontaneously Hypertensive Rats

Abstract

BackgroundChronic hypertension causes a state of inflammation and leads to vascular remodeling. Vascular remodeling involves alterations in vascular smooth muscle cells, endothelium, and extracellular matrix. Collagen deposition is increased in conductance and resistance vessels of hypertensive animals.Fibrocytes are bone marrow‐derived cells found in the circulation that migrate toward injured tissue. At the injured site, fibrocytes contribute to healing by serving as antigen presenting cells and secrete cytokines such as IL‐6 and IL‐8 to recruit T cells. Fibrocytes also lay down extracellular matrix such as collagen, and its activation is implicated in many fibrotic diseases including cardiac fibrosis. Studies have shown that patients with hypertensive heart disease have increased number of circulating fibrocytes and that hearts of hypertensive patients have increased collagen levels. The role of fibrocytes in vascular remodeling in hypertension have not been investigated.HypothesisThis study tests the hypothesis that fibrocytes are increased in hypertension and play a role in vascular remodeling.MethodsMale spontaneously hypertensive rats (SHR) and Wistar rats 13–16 weeks old were used in this study. Flow cytometry was used to determine the percentage of fibrocytes (CD34+/CD45+/CollagenI+) in the peripheral blood, aorta, mesenteric resistance arteries (MRA), and pudendal arteries. Wire myograph was used to evaluate the differences in vascular function in response to phenylephrine (PE), norepinephrine (NE), acetylcholine (ACh), and sodium nitroprusside (SNP) between SHR and Wistar. Immunohistochemistry was used to detect fibrocytes (CD34+/CD45+/Collagen I+) within the vascular walls of aorta, mesenteric, and pudendal arteries. Statistical analysis performed using nonlinear regression, two‐tailed unpaired t‐test, and two‐way ANOVA.ResultsFlow cytometry did not show a difference between the percentage of fibrocytes in SHR compared to Wistar. Wire myography demonstrated differences between the two groups in aortic contraction to PE (p<0.0001) and NE (p<0.0001), aortic relaxation to ACh (p<0.0001) and SNP (p<0.0001), MRA relaxation to ACh (p<0.0001), and pudendal artery relaxation to SNP (p<0.0001). Immunohistochemistry showed increased number of fibrocytes in the media layer of the SHR aorta (Figure 1) compared to Wistar (Figure 2).ConclusionsThe number of fibrocytes are increased in the media layer in the aorta in SHR compared to Wistar. The increased number of fibrocytes may contribute to increased collagen deposition leading to decreased vascular compliance in hypertensive animals.Support or Funding InformationNIH P01 HL‐134604This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.