Submission
| Title: | Assessing Expression Profile of Adrenergic Receptors in Human Hearts from Patients with CKD |
| Presenter: | Leonardo Alarcon |
| Institution: | Ivy Tech Community College |
| Authors: | ¹Leonardo Alarcon ²Arvin Halim ²Dr. Monique Campos, PhD ²Dr. Kenneth Lim, MD PhD 1. Ivy Tech Community College, Indianapolis, IN 2. Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, IN |
Abstract
| Background/Significance/Rationale: | Chronotropic incompetence (CI), defined as an impaired heart rate (HR) response to exercise, leads to a higher risk of mortality in patients with chronic kidney disease (CKD). In individuals without CKD, elevated catecholamines from autonomic dysfunction leads to downregulation of β1-adrenergic receptors (β1-ARs), which are essential for regulating HR. Moreover, decreased β1-ARs function is associated with upregulation of α1-ARs, which is purported to be a cardioprotective and compensatory response to chronic stress. In CKD, catecholamines are also elevated, but how cardiac ARs are affected in CKD is unknown. Therefore, we aim to comprehensively phenotype the ARs expression in the donor hearts of patients with CKD. |
| Methods: | A cross-sectional study was conducted involving 45 donated human left ventricular (LV) tissue samples of patients with advanced CKD (Hemodialysis, HD; n=18), hypertensive controls with preserved kidney function (HTN; n=10), and healthy controls (CON; n=17), from the Cardiovascular Aging in CKD (CAIN) cohort. Tissues were subjected to immunoblotting and bulk RNA sequencing. |
| Results/Findings: | β1-AR protein expression was similar across all groups. Two α1a-AR isoforms were detected at 50kDa and 32kDa. 32 kDa α1a-AR was elevated in both HD and HTN groups compared to the CON group (P<0.05, P<0.001), but there was no difference between HTN and HD groups. 50 kDa α1a-AR expression was similar across all groups. Additionally, RNAseq showed no differential expression of AR signaling-related genes (FDR > 0.05). |
| Conclusions/Discussion: | Our data suggests β1-AR expression is unchanged in hearts from HD patients in our cohort. Additionally, upregulation of the 32kDa α1a-AR isoform in CKD hearts suggests CKD hearts also undergo compensatory mechanisms. Further studies are needed to validate these findings and whether CI in CKD may originate from impaired downstream β1-AR signaling. |
| Translational/Human Health Impact: | Elucidating the expression profile of ARs in CKD hearts will provide further insight into the underlying mechanisms of and possible therapeutic targets for CI in patients with CKD. |
