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Article: Commentary: Transforming growth factor serum concentrations in patients with proven non-syndromic aortopathy.

Grewal, Nimrat / Klautz, Robert / Poelmann, Robert E

2023 Volume 10, Page(s) 1097201

Language	English
Publishing date	2023-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1097201
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Article ; Online: Sex Differences in the Histopathology of Acute Type A Aortic Dissections.

Grewal, Nimrat / Dolmaci, Onur Baris / Klautz, Robert Jm / Poelmann, Robert E

The Thoracic and cardiovascular surgeon

2024

Abstract: Background: Although sex-related differences in cardiovascular surgery outcomes have increasingly garnered attention in the past decades, knowledge about sex disparities in the pathophysiology of acute type A aortic dissections (ATAADs) remains sparse. ...

Abstract	Background: Although sex-related differences in cardiovascular surgery outcomes have increasingly garnered attention in the past decades, knowledge about sex disparities in the pathophysiology of acute type A aortic dissections (ATAADs) remains sparse. In this study, we evaluate the histopathologic and atherosclerotic lesions in female and male ATAAD patients. Methods: A total of 68 patients were studied: 51 ATAAD patients (mean age: 62.5 ± 10.8 years; 49% women) and 17 control patients (mean age: 63 ± 5.5 years; 53% women). Cardiovascular risk factors were assessed clinically. Intimal and medial histopathological features were systematically evaluated in all. Results: Compared to the control group, all ATAAD patients showed significantly more elastic fiber pathology, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration ( Conclusion: All ATAAD patients had a significantly thinner tunica intima and significantly diseased tunica media compared to the control patients. Our results suggest that the severity of medial aortic pathology is not sex specific in ATAAD patients. Intimal differences between females and males could, however, be considered a potential risk factor for the development of an aortic dissection.
Language	English
Publishing date	2024-02-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	800050-5
ISSN	1439-1902 ; 0171-6425 ; 0946-4778 ; 0172-6137
ISSN (online)	1439-1902
ISSN	0171-6425 ; 0946-4778 ; 0172-6137
DOI	10.1055/a-2239-1741
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Article ; Online: Intrinsic histological and morphological abnormalities of the pediatric thoracic aorta in bicuspid aortic valve patients are predictive for future aortopathy.

Grewal, Nimrat / Klautz, Robert J M / Poelmann, Robert E

Pathology, research and practice

2023 Volume 248, Page(s) 154620

Abstract: Background: Patients with a bicuspid aortic valve (BAV) have an increased risk to develop aortic complications. Many studies are pointing towards a possible embryonic explanation for the development of both a bicuspid aortic valve as well as a defective ...

Abstract	Background: Patients with a bicuspid aortic valve (BAV) have an increased risk to develop aortic complications. Many studies are pointing towards a possible embryonic explanation for the development of both a bicuspid aortic valve as well as a defective ascending aortic wall in these patients. The fetal and newborn ascending aortic wall has however scarcely been studied in bicuspid aortic valve patients. We hypothesize that early histopathological defects might already be visible in the fetal and pediatric ascending aortic wall of bicuspid aortic valve patients, indicating at an early embryonic defect. Methods: Non-dilated BAV ascending aortic wall samples were collected (n = 40), categorized in five age groups: premature (age range 17.5 weeks + days GA till 37.6 weeks + days GA) 2. neonate (age range 1 - 21 days) 3. infant (age range 1 month - 4 years) 4. adolescent (age range 12 years - 15 years) and 5. adult (age range 41 - 72 years). Specimen were studied for intimal and medial histopathological features. Results: The premature ascending aortic wall has a significantly thicker intimal and significantly thinner medial layer as compared to all other age categories (p < 0.05). After birth the intimal thickness decreases significantly. The medial layer increases in thickness before adulthood (p < 0.05) with an increasing number of elastic lamellae (p < 0.01) and interlamellar mucoid extracellular matrix accumulation (p < 0.0001). Intimal atherosclerosis was scarce and medial histopathological features such as overall medial degeneration, smooth muscle cell nuclei loss and elastic fiber fragmentation were not appreciated in the BAV ascending aortic wall of any age. Conclusions: The main characteristics of a bicuspid ascending aortic wall are already present before adulthood, albeit not before birth. Considering the early manifestations of ascending aortic wall pathology in bicuspid aortic valve patients, the pediatric population should be considered while searching for markers predictive for future aortopathy.
MeSH term(s)	Adult ; Infant, Newborn ; Adolescent ; Humans ; Child ; Infant ; Middle Aged ; Aged ; Bicuspid Aortic Valve Disease/complications ; Bicuspid Aortic Valve Disease/pathology ; Aorta, Thoracic/pathology ; Aortic Valve/pathology ; Heart Valve Diseases/complications ; Heart Valve Diseases/pathology ; Aorta/pathology
Language	English
Publishing date	2023-06-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.154620
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Article ; Online: Can transforming growth factor beta and downstream signalers distinguish bicuspid aortic valve patients susceptible for future aortic complications?

Grewal, Nimrat / Klautz, Robert / Poelmann, Robert E

Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology

2022 Volume 63, Page(s) 107498

Abstract: Patients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of deaths being preventable if individuals at risk are ... ...

Abstract	Patients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of deaths being preventable if individuals at risk are identified and properly managed. Risk stratification for TAADs in bicuspidy is so far solely based on the aortic diameter. Exclusive use of aortic wall dimension, as in the current guidelines, is however not sufficient in selecting patients vulnerable for future aortic wall complications. Moreover, there are no effective medical treatments for TAADs to retain progressive aortic dilatation and thus prevent or delay aortic complications. Only surgical replacement of the aorta increases life expectancy in patients with a risk for a TAAD. Therefore, the next major challenge in the management of TAADs is the development of a personalized patient-tailored risk stratification for early detection of patients with an increased risk for TAADs, who will benefit from surgical resection of the aorta. Several signaling pathways have been studied in recent times to develop a patient specific risk stratification model. In this paper we discuss TGF-β signaling and downstream signalers as potential markers for future aortic complications in bicuspid aortic valve patients.
MeSH term(s)	Humans ; Aorta/pathology ; Aortic Dissection/genetics ; Aortic Dissection/metabolism ; Aortic Valve/surgery ; Aortic Valve/metabolism ; Bicuspid Aortic Valve Disease/complications ; Bicuspid Aortic Valve Disease/genetics ; Bicuspid Aortic Valve Disease/metabolism ; Bicuspid Aortic Valve Disease/pathology ; Bicuspid Aortic Valve Disease/surgery ; Signal Transduction ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism
Chemical Substances	TGFB1 protein, human ; Transforming Growth Factor beta
Language	English
Publishing date	2022-11-18
Publishing country	United States
Document type	Editorial
ZDB-ID	1134600-0
ISSN	1879-1336 ; 1054-8807
ISSN (online)	1879-1336
ISSN	1054-8807
DOI	10.1016/j.carpath.2022.107498
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Article ; Online: Can general histopathology distinguish bicuspid aortopathy?

Grewal, Nimrat / Driessen, Antoine / Klautz, Robert J M / Poelmann, Robert E

Journal of cardiac surgery

2022

Language	English
Publishing date	2022-11-06
Publishing country	United States
Document type	Editorial
ZDB-ID	639059-6
ISSN	1540-8191 ; 0886-0440
ISSN (online)	1540-8191
ISSN	0886-0440
DOI	10.1111/jocs.17103
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Article ; Online: Introduction to Special Issue "Leaders in Cardiovascular Research, Dedicated to the Memory of Professor Adriana Gittenberger-de Groot".

Gittenberger, Edi / Poelmann, Robert E / Jongbloed, Monique R M

Journal of cardiovascular development and disease

2022 Volume 9, Issue 4

Abstract: This Introduction provides both a short reflection on the scientific career of Adriana Gittenberger-de Groot and an overview of the papers that form the basis of this Special Issue giving them a proper perspective. The papers have as a central focus the ... ...

Abstract	This Introduction provides both a short reflection on the scientific career of Adriana Gittenberger-de Groot and an overview of the papers that form the basis of this Special Issue giving them a proper perspective. The papers have as a central focus the outflow tract, and include contributions on development and pathology of the ventricles including AV valves, as well as developmental and pathomorphological aspects of the great arteries including semilunar valves and coronary arteries.
Language	English
Publishing date	2022-03-23
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2777082-5
ISSN	2308-3425 ; 2308-3425
ISSN (online)	2308-3425
ISSN	2308-3425
DOI	10.3390/jcdd9040092
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Article: Sex Differences in the Histopathology of Acute Type A Aortic Dissections

Grewal, Nimrat / Dolmaci, Onur Baris / Klautz, Robert JM / Poelmann, Robert E.

The Thoracic and Cardiovascular Surgeon

2024

Abstract	Background: Although sex-related differences in cardiovascular surgery outcomes have increasingly garnered attention in the past decades, knowledge about sex disparities in the pathophysiology of acute type A aortic dissections (ATAADs) remains sparse. In this study, we evaluate the histopathologic and atherosclerotic lesions in female and male ATAAD patients. Methods: A total of 68 patients were studied: 51 ATAAD patients (mean age: 62.5 ± 10.8 years; 49% women) and 17 control patients (mean age: 63 ± 5.5 years; 53% women). Cardiovascular risk factors were assessed clinically. Intimal and medial histopathological features were systematically evaluated in all. Results: Compared to the control group, all ATAAD patients showed significantly more elastic fiber pathology, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration ( p < 0.0001). The tunica intima was significantly thinner in the ATAAD patients than in the control group ( p < 0.023), with the latter exhibiting significantly more progressive atherosclerotic lesions than the former. No difference in medial vessel wall pathology was seen between female and male patients. As compared to male ATAAD patients, atherosclerotic lesions were more severe in female ATAAD patients, independent of age and the cardiovascular risk factor hypertension. Conclusion: All ATAAD patients had a significantly thinner tunica intima and significantly diseased tunica media compared to the control patients. Our results suggest that the severity of medial aortic pathology is not sex specific in ATAAD patients. Intimal differences between females and males could, however, be considered a potential risk factor for the development of an aortic dissection.
Keywords	aorta ; dissection ; sex differences ; histopathology
Language	English
Publishing date	2024-01-05
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	800050-5
ISSN	1439-1902 ; 0171-6425 ; 0946-4778 ; 0172-6137
ISSN (online)	1439-1902
ISSN	0171-6425 ; 0946-4778 ; 0172-6137
DOI	10.1055/a-2239-1741
Database	Thieme publisher's database

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Article: Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease.

Grewal, Nimrat / Dolmaci, Onur / Jansen, Evert / Klautz, Robert / Driessen, Antoine / Poelmann, Robert E

Frontiers in cardiovascular medicine

2023 Volume 10, Page(s) 1018167

Abstract: Background: Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of ... ...

Abstract	Background: Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine. Objective: This study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals. Materials and methods: Bicuspid aortic valve (BAV; Results: The MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima ( Conclusion: This study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.
Language	English
Publishing date	2023-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1018167
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Article: Are acute type A aortic dissections atherosclerotic?

Grewal, Nimrat / Dolmaci, Onur / Jansen, Evert / Klautz, Robert / Driessen, Antoine / Lindeman, Jan / Poelmann, Robert E

Frontiers in cardiovascular medicine

2023 Volume 9, Page(s) 1032755

Abstract: Background: Type A aortic dissections (TAAD) are devastating aortic complications. Patients with Marfan syndrome, a bicuspid aortic valve or a thoracic aortic aneurysm have an increased risk to develop a TAAD. These predisposing conditions are ... ...

Abstract	Background: Type A aortic dissections (TAAD) are devastating aortic complications. Patients with Marfan syndrome, a bicuspid aortic valve or a thoracic aortic aneurysm have an increased risk to develop a TAAD. These predisposing conditions are characterized by a histologically thin intimal layer and hardly any atherosclerosis. Little is known about the susceptibility for atherosclerosis in patients with a type A aortic dissection. Objective: We aim to systematically describe atherosclerotic lesions in TAAD patients. Materials and methods: A total of 51 patients with a TAAD (mean age 62.5 ± 10.8 years, 49% females) and 17 control patients (mean age 63 ± 5.5 years, 53% females) were included in this study. Cardiovascular risk factors were assessed clinically. All sections were stained with Movat pentachrome and hematoxylin eosin. Plaque morphology was classified according to the modified AHA classification scheme proposed by Virmani et al. Results: In the TAAD group thirty-seven percent were overweight (BMI > 25). Diabetes and peripheral arterial disease were not present in any of the patients. Fifty-nine percent of the patients had a history of hypertension. The intima in TAAD patients was significantly thinner as compared to the control group (mean thickness 143 ± 126.5 μm versus 193 ± 132 μm, Discussion: This study shows that TAAD patients hardly exhibit any form of progressive atherosclerosis. The majority of TAAD patients showcase non-progressive intimal lesions, whereas the control group mostly demonstrated progressive intimal atherosclerotic lesions. Findings are independent of age, sex, or the presence of (a history of) hypertension.
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.1032755
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Article ; Online: Thoracic aortic atherosclerosis in patients with a bicuspid aortic valve; a case-control study.

Dolmaci, Onur B / Klautz, Robert J M / Poelmann, Robert E / Lindeman, Jan H N / Sprengers, Ralf / Kroft, Lucia / Grewal, Nimrat

BMC cardiovascular disorders

2023 Volume 23, Issue 1, Page(s) 363

Abstract: Introduction: Bicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV ascending aortic wall. This study evaluates and compares ... ...

Abstract	Introduction: Bicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV ascending aortic wall. This study evaluates and compares the prevalence of thoracic aortic atherosclerosis in BAV and tricuspid aortic valve (TAV) patients. Methods: Atherosclerosis was objectified using three diagnostic modalities in two separate BAV patient cohorts (with and without an aortic dilatation). Within the first group, atherosclerosis was graded histopathologically according to the modified AHA classification scheme proposed by Virmani et al. In the second group, the calcific load of the ascending aorta and coronary arteries, coronary angiographies and cardiovascular risk factors were studied. Patients were selected from a surgical database (treated between 2006-2020), resulting in a total of 128 inclusions. Results: Histopathology showed atherosclerotic lesions to be more prevalent and severe in all TAV as compared to all BAV patients (OR 1.49 (95%CI 1.14 - 1.94); p = 0.003). Computed tomography showed no significant differences in ascending aortic wall calcification between all BAV and all TAV patients, although a tendency of lower calcific load in favor of BAV was seen. Coronary calcification was higher in all TAV as compared to all BAV (OR 1.30 (95%CI 1.06 - 1.61); p = 0.014). Conclusion: Ascending aortic atherosclerotic plaques were histologically more pronounced in TAV as compared to the BAV patients, while CT scans revealed equal amounts of calcific depositions within the ascending aortic wall. This study confirms less atherosclerosis in the ascending aortic wall and coronary arteries of BAV patients as compared to TAV patients. These results were not affected by the presence of a thoracic aortic aneurysm.
MeSH term(s)	Humans ; Bicuspid Aortic Valve Disease/complications ; Heart Valve Diseases/diagnostic imaging ; Heart Valve Diseases/epidemiology ; Heart Valve Diseases/complications ; Case-Control Studies ; Aortic Valve/surgery ; Aortic Diseases/diagnostic imaging ; Aortic Diseases/epidemiology ; Aortic Diseases/complications ; Atherosclerosis/diagnostic imaging ; Atherosclerosis/epidemiology
Language	English
Publishing date	2023-07-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2059859-2
ISSN	1471-2261 ; 1471-2261
ISSN (online)	1471-2261
ISSN	1471-2261
DOI	10.1186/s12872-023-03396-4
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