Concurrent left ventricular pressure-loading improves right ventricular function, remodeling, and molecular signaling in response to pulmonary artery banding Article Swipe
Xavier Lee
,
Sonja Raschzok
,
J. Desjardins
,
Omar Kanny
,
Golam Kabir
,
Linda Nghiem
,
András Kapùs
,
Kim A. Connelly
,
Mark K. Friedberg
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/eurheartj/ehad655.3216
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/eurheartj/ehad655.3216
Background Studies have established the significance of right ventricle (RV) function in individuals with many congenital heart diseases, however the impact of pressure overload (PO) on the RV, concomitant with changes in LV pressure, has yet to be fully understood. We have previously demonstrated that pulmonary artery banding (PAB) with simultaneous LVPO improved systolic function in both ventricles and reduced myocyte hypertrophy and collagen content compared to PAB alone1. These findings suggested that increasing LV afterload attenuated maladaptive RV remodeling and molecular signaling. Purpose We investigated whether the degree of LV afterload beneficially impacts RV function, remodeling, and molecular signaling pathways. Methods We established a model of double-banding (DB) in male Sprague-Dawley rats (n = 17) where the PA and transverse aorta were constricted with 16-gauge and 14-gauge needles, respectively. At 6-weeks post-surgery, Doppler-echocardiography was used to measure the flow velocity across the aortic constriction to divide the DB rats into moderate (DBMOD) and mild (DBMILD) groups. PAB-only (n=9) and Sham (n=9) groups were used as controls. All animals underwent echocardiography and cardiac catheterization 6-weeks post-surgery to assess RV/LV structure and hemodynamic function. Heart tissue was collected for Picrosirius red (PSR) staining to assess RV collagen content. Immunoblotting and RT-qPCR were used to quantify protein and transcripts of fibrosis and mechanotransduction pathways. Results Echocardiography identified increases in RV end-diastolic and end-systolic areas alongside a decrease in tricuspid annular plane systolic excursion (TAPSE) in PAB rats compared to shams. These changes were abrogated in DBMOD rats and to a lesser extent in DBMILD rats (p<0.001). Hemodynamic analyses identified significantly increased dP/dtmax/min, and end-systolic pressure-volume relationship in the PAB group, each of which returned to near-Sham levels in the DBMOD group (p<0.0001). PSR-staining revealed a significant decrease of RV fibrosis in the DBMOD group compared to PAB rats (p<0.05). Immunoblotting in RV tissue revealed increases in myocardin-related transcription factor A, and YAP/TAZ in PAB rats; protein expression returned to near-sham levels in the DBMOD group (p<0.05) with an intermediate expression in the DBMILD group (p<0.05). RT-qPCR of RV tissue revealed significantly increased collagen 1&3, TGFβ1, and CTGF transcripts which returned to baseline in the DBMOD group (p<0.05). Conclusion Our results indicate that the degree of LV pressure provides a beneficial impact on RV function, remodeling, and both Hippo and profibrotic signaling during RV PO. Our study demonstrates the importance of ventricular interdependence from a physiological and molecular level and suggests that modulating LV pressures during diseases that impact the RV (such as pulmonary hypertension) offer a potentially attractive therapeutic route.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/eurheartj/ehad655.3216
- https://academic.oup.com/eurheartj/article-pdf/44/Supplement_2/ehad655.3216/53590323/ehad655.3216.pdf
- OA Status
- bronze
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388597836
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4388597836Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/eurheartj/ehad655.3216Digital Object Identifier
- Title
-
Concurrent left ventricular pressure-loading improves right ventricular function, remodeling, and molecular signaling in response to pulmonary artery bandingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-01Full publication date if available
- Authors
-
Xavier Lee, Sonja Raschzok, J. Desjardins, Omar Kanny, Golam Kabir, Linda Nghiem, András Kapùs, Kim A. Connelly, Mark K. FriedbergList of authors in order
- Landing page
-
https://doi.org/10.1093/eurheartj/ehad655.3216Publisher landing page
- PDF URL
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https://academic.oup.com/eurheartj/article-pdf/44/Supplement_2/ehad655.3216/53590323/ehad655.3216.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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bronzeOpen access status per OpenAlex
- OA URL
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https://academic.oup.com/eurheartj/article-pdf/44/Supplement_2/ehad655.3216/53590323/ehad655.3216.pdfDirect OA link when available
- Concepts
-
Medicine, Pressure overload, Internal medicine, Cardiology, Afterload, Ventricle, Ventricular remodeling, Pulmonary artery, Ventricular pressure, Hemodynamics, Diastole, Pulmonary hypertension, Cardiac function curve, Pulmonary artery banding, Aorta, Systole, Heart failure, Blood pressure, Cardiac hypertrophyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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