Your browser doesn't support javascript.
Marked Up-Regulation of ACE2 in Hearts of Patients With Obstructive Hypertrophic Cardiomyopathy: Implications for SARS-CoV-2-Mediated COVID-19.
Bos, J Martijn; Hebl, Virginia B; Oberg, Ann L; Sun, Zhifu; Herman, Daniel S; Teekakirikul, Polakit; Seidman, Jonathan G; Seidman, Christine E; Dos Remedios, Cristobal G; Maleszewski, Joseph J; Schaff, Hartzell V; Dearani, Joseph A; Noseworthy, Peter A; Friedman, Paul A; Ommen, Steve R; Brozovich, Frank V; Ackerman, Michael J.
  • Bos JM; Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN.
  • Hebl VB; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
  • Oberg AL; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
  • Sun Z; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
  • Herman DS; Department of Genetics, Harvard Medical School, Boston, MA.
  • Teekakirikul P; Department of Genetics, Harvard Medical School, Boston, MA.
  • Seidman JG; Department of Genetics, Harvard Medical School, Boston, MA.
  • Seidman CE; Department of Genetics, Harvard Medical School, Boston, MA; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA; Howard Hughes Medical Institute, Chevy Chase, MD.
  • Dos Remedios CG; Mechanobiology Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
  • Maleszewski JJ; Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN.
  • Schaff HV; Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN.
  • Dearani JA; Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN.
  • Noseworthy PA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
  • Friedman PA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
  • Ommen SR; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
  • Brozovich FV; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
  • Ackerman MJ; Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN; Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine
Mayo Clin Proc ; 95(7): 1354-1368, 2020 07.
Article in English | MEDLINE | ID: covidwho-1500136
Semantic information from SemMedBD (by NLM)
1. Heart PART_OF Patients
Subject
Heart
Predicate
PART_OF
Object
Patients
2. Hypertrophic obstructive cardiomyopathy PROCESS_OF Patients
Subject
Hypertrophic obstructive cardiomyopathy
Predicate
PROCESS_OF
Object
Patients
3. ACE2 gene|ACE2 AUGMENTS Heart
Subject
ACE2 gene|ACE2
Predicate
AUGMENTS
Object
Heart
4. 2019 novel coronavirus INTERACTS_WITH COVID-19
Subject
2019 novel coronavirus
Predicate
INTERACTS_WITH
Object
COVID-19
5. Hypertrophic Cardiomyopathy PROCESS_OF Patients
Subject
Hypertrophic Cardiomyopathy
Predicate
PROCESS_OF
Object
Patients
6. Heart PART_OF Tissue Donors
Subject
Heart
Predicate
PART_OF
Object
Tissue Donors
7. Heart tissue LOCATION_OF Flash
Subject
Heart tissue
Predicate
LOCATION_OF
Object
Flash
8. Septal myectomy TREATS Hypertrophic Cardiomyopathy
Subject
Septal myectomy
Predicate
TREATS
Object
Hypertrophic Cardiomyopathy
9. Septal myectomy TREATS Patients
Subject
Septal myectomy
Predicate
TREATS
Object
Patients
10. Bioanalytical Validation Method USES Real-Time Polymerase Chain Reaction
Subject
Bioanalytical Validation Method
Predicate
USES
Object
Real-Time Polymerase Chain Reaction
11. ACE2 gene|ACE2 INTERACTS_WITH Angiotensins
Subject
ACE2 gene|ACE2
Predicate
INTERACTS_WITH
Object
Angiotensins
12. Genes ASSOCIATED_WITH Hypertrophic Cardiomyopathy
Subject
Genes
Predicate
ASSOCIATED_WITH
Object
Hypertrophic Cardiomyopathy
13. ACE2 gene|ACE2 STIMULATES Genes
Subject
ACE2 gene|ACE2
Predicate
STIMULATES
Object
Genes
14. Heart LOCATION_OF ACE2 gene|ACE2
Subject
Heart
Predicate
LOCATION_OF
Object
ACE2 gene|ACE2
15. ACE2 gene|ACE2 STIMULATES Proteins
Subject
ACE2 gene|ACE2
Predicate
STIMULATES
Object
Proteins
16. Increased risk PROCESS_OF Patients
Subject
Increased risk
Predicate
PROCESS_OF
Object
Patients
17. Heart PART_OF Patients
Subject
Heart
Predicate
PART_OF
Object
Patients
18. Hypertrophic obstructive cardiomyopathy PROCESS_OF Patients
Subject
Hypertrophic obstructive cardiomyopathy
Predicate
PROCESS_OF
Object
Patients
19. ACE2 gene|ACE2 AUGMENTS Heart
Subject
ACE2 gene|ACE2
Predicate
AUGMENTS
Object
Heart
20. 2019 novel coronavirus INTERACTS_WITH COVID-19
Subject
2019 novel coronavirus
Predicate
INTERACTS_WITH
Object
COVID-19
21. Hypertrophic Cardiomyopathy PROCESS_OF Patients
Subject
Hypertrophic Cardiomyopathy
Predicate
PROCESS_OF
Object
Patients
22. Heart PART_OF Tissue Donors
Subject
Heart
Predicate
PART_OF
Object
Tissue Donors
23. Heart tissue LOCATION_OF Flash
Subject
Heart tissue
Predicate
LOCATION_OF
Object
Flash
24. Septal myectomy TREATS Hypertrophic Cardiomyopathy
Subject
Septal myectomy
Predicate
TREATS
Object
Hypertrophic Cardiomyopathy
25. Septal myectomy TREATS Patients
Subject
Septal myectomy
Predicate
TREATS
Object
Patients
26. Bioanalytical Validation Method USES Real-Time Polymerase Chain Reaction
Subject
Bioanalytical Validation Method
Predicate
USES
Object
Real-Time Polymerase Chain Reaction
27. ACE2 gene|ACE2 INTERACTS_WITH Angiotensins
Subject
ACE2 gene|ACE2
Predicate
INTERACTS_WITH
Object
Angiotensins
28. Genes ASSOCIATED_WITH Hypertrophic Cardiomyopathy
Subject
Genes
Predicate
ASSOCIATED_WITH
Object
Hypertrophic Cardiomyopathy
29. ACE2 gene|ACE2 STIMULATES Genes
Subject
ACE2 gene|ACE2
Predicate
STIMULATES
Object
Genes
30. Heart LOCATION_OF ACE2 gene|ACE2
Subject
Heart
Predicate
LOCATION_OF
Object
ACE2 gene|ACE2
31. ACE2 gene|ACE2 STIMULATES Proteins
Subject
ACE2 gene|ACE2
Predicate
STIMULATES
Object
Proteins
32. Increased risk PROCESS_OF Patients
Subject
Increased risk
Predicate
PROCESS_OF
Object
Patients
ABSTRACT

OBJECTIVE:

To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls. PATIENTS AND

METHODS:

RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All patients with HCM were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. This study was started on January 1, 1999, and final analysis was completed on April 20, 2020.

RESULTS:

Overall, 22% of the transcriptome (8443 of 37,846 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4% (1502 of 37,846) to 6% (2336 of 37,846) of the transcriptome exhibiting differential expression between genotypic subgroups. The qRT-PCR confirmed differential expression in 92% (11 of 12 genes) of tested transcripts. Notably, in the context of coronavirus disease 2019 (COVID-19), the transcript for angiotensin I converting enzyme 2 (ACE2), a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change, 3.53; q-value =1.30×10-23), which was confirmed by qRT-PCR in triplicate (fold change, 3.78; P=5.22×10-4), and Western blot confirmed greater than 5-fold overexpression of ACE2 protein (fold change, 5.34; P=1.66×10-6).

CONCLUSION:

More than 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM, indicating perhaps the heart's compensatory effort to mount an antihypertrophic, antifibrotic response. However, given that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Cardiomyopathy, Hypertrophic / Coronavirus Infections / Peptidyl-Dipeptidase A / Betacoronavirus Type of study: Observational study / Risk factors Limits: Adolescent / Adult / Aged / Child / Humans / Middle aged / Young adult Language: English Journal: Mayo Clin Proc Year: 2020 Document Type: Article Affiliation country: J.mayocp.2020.04.028

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Cardiomyopathy, Hypertrophic / Coronavirus Infections / Peptidyl-Dipeptidase A / Betacoronavirus Type of study: Observational study / Risk factors Limits: Adolescent / Adult / Aged / Child / Humans / Middle aged / Young adult Language: English Journal: Mayo Clin Proc Year: 2020 Document Type: Article Affiliation country: J.mayocp.2020.04.028