scholarly journals Genetic Background Dictates Aortic Fibrosis in Hypertensive Mice

2019 ◽  
Author(s):  
Bart Spronck ◽  
Marcos Latorre ◽  
Sameet Mehta ◽  
Alexander W. Caulk ◽  
Abhay B. Ramachandra ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Wall Stress ◽  
Biomechanical Properties ◽  
Background Strain ◽  
Induced Hypertension ◽  
Before And After ◽  
Mechanical Homeostasis ◽  
And Function ◽  
Aortic Remodeling ◽  
Muscle Contractile

AbstractMany genetic mutations affect aortic structure and function in mice, but little is known about the influence of background strain. We phenotyped aortas from C57BL/6J and 129SvEv mice before and after continuous infusion of angiotensin II (AngII) for two weeks, which elevated blood pressure similarly in both strains (1.34-fold vs. 1.32-fold, systolic). Excised thoracic aortas were characterized functionally using isobaric vasoactive and cyclic passive stiffness tests whereas immunohistological studies quantified altered medial and adventitial composition as well as the infiltration of pan-inflammatory CD45+ cells. Baseline aortic geometry, composition, and biomechanical properties were similar across strains, consistent with mechanical homeostasis. Yet, aortic remodeling in response to AngII-induced hypertension differed dramatically between strains, with gross maladaptive remodeling in C57BL/6J but not in 129SvEv mice. CD45+ cell density was markedly higher in C57BL/6J than 129SvEv aortas while vasoconstrictive responses to AngII were greater in 129SvEv than C57BL/6J both before and after hypertension; importantly, smooth muscle mediated vasoconstriction reduces pressure-induced wall stress. Bulk RNA sequencing, layer-specific biomechanical modeling, and growth and remodeling simulations support the emergent hypothesis that mechanical stress-mediated immune processes promote maladaptive remodeling while smooth muscle contractile processes reduce wall stress and thereby protect against fibrosis. Differentially expressed mechano-sensitive genes thus play key roles in the distinct hypertensive aortic remodeling in C57BL/6J and 129SvEv mice and must be considered when comparing studies in different background strains, particularly mixed strains that are often used to generate mice with targeted mutations.Graphical Abstract

scholarly journals Maladaptive aortic remodeling in hypertension associates with dysfunctional smooth muscle contractility

2019 ◽  
Vol 316 (2) ◽  
pp. H265-H278 ◽  
Author(s):  
Arina Korneva ◽  
Jay D. Humphrey
Keyword(s):  
Smooth Muscle ◽  
Structural Integrity ◽  
Wall Stress ◽  
Elevated Pressure ◽  
Smooth Muscle Contractility ◽  
Experimental Conditions ◽  
Pressure Elevation ◽  
Material Stiffness ◽  
And Function ◽  
Aortic Remodeling

Intramural cells are responsible for establishing, maintaining, and restoring the functional capability and structural integrity of the aortic wall. In response to hypertensive loading, these cells tend to increase wall content via extracellular matrix turnover in an attempt to return wall stress and/or material stiffness toward homeostatic values despite the elevated pressure. Using a common rodent model of induced hypertension, we found marked mouse-to-mouse differences in thoracic aortic remodeling over 2–4 wk of pressure elevation, with mechanoadaptation in some but gross maladaptation in most mice despite the same experimental conditions and overall genetic background. Consistent with our hypothesis, we also found a strong correlation between maladaptive aortic remodeling and a dysfunctional ability of the vessel to vasoconstrict, with maladaptation often evidenced by marked adventitial fibrosis. Remarkably, mouse-to-mouse variability did not correlate with the degree or duration of pressure elevation over the 2- to 4-wk study period. These findings suggest both a need to study together the structure, mechanical properties, and function across layers of the wall when assessing aortic health and a need for caution in using common statistical comparisons across small seemingly well-defined groups that may mask important underlying individual responses, an area of investigation that demands increasing attention as we move toward an era of precision diagnosis and patient care. NEW & NOTEWORTHY There are three primary findings. Marked mouse-to-mouse differences exist in large vessel hypertensive remodeling in an otherwise equivalent cohort of animals. The degree of maladaptation correlates strongly with decreases in smooth muscle contractile capacity. Finally, short-term maladaptive remodeling is independent of the precise degree or duration of the pressure elevation provided that thresholds are exceeded. Therapeutic targets should thus be personalized and focus on both layer-to-layer interactions and early interventions.

scholarly journals Complementary roles of mechanotransduction and inflammation in vascular homeostasis

2021 ◽  
Vol 477 (2245) ◽  
pp. 20200622
Author(s):  
Marcos Latorre ◽  
Bart Spronck ◽  
Jay D. Humphrey
Keyword(s):  
Theoretical Model ◽  
Vascular Health ◽  
Induced Hypertension ◽  
Health And Disease ◽  
Vascular Geometry ◽  
Mechanical Homeostasis ◽  
Using Data ◽  
And Function ◽  
Insight Into ◽  
Structure Properties

Arteries are exposed to relentless pulsatile haemodynamic loads, but via mechanical homeostasis they tend to maintain near optimal structure, properties and function over long periods in maturity in health. Numerous insults can compromise such homeostatic tendencies, however, resulting in maladaptations or disease. Chronic inflammation can be counted among the detrimental insults experienced by arteries, yet inflammation can also play important homeostatic roles. In this paper, we present a new theoretical model of complementary mechanobiological and immunobiological control of vascular geometry and composition, and thus properties and function. We motivate and illustrate the model using data for aortic remodelling in a common mouse model of induced hypertension. Predictions match the available data well, noting a need for increased data for further parameter refinement. The overall approach and conclusions are general, however, and help to unify two previously disparate literatures, thus leading to deeper insight into the separate and overlapping roles of mechanobiology and immunobiology in vascular health and disease.

Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle

2020 ◽  
Vol 882 ◽  
pp. 173281 ◽  
Author(s):  
Vladimir Djokic ◽  
Svetlana Jankovic ◽  
Milica Labudovic-Borovic ◽  
Jelena Rakocevic ◽  
Jelena Stanisic ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Potassium Channel ◽  
Umbilical Vein ◽  
Pregnancy Induced Hypertension ◽  
Human Umbilical Vein ◽  
Induced Hypertension ◽  
Channel Expression ◽  
And Function

scholarly journals Vascular smooth muscle phenotypic diversity and function

2010 ◽  
Vol 42A (3) ◽  
pp. 169-187 ◽  
Author(s):  
Steven A. Fisher
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Function ◽  
Striated Muscle ◽  
Vascular System ◽  
Mechanical Load ◽  
Phenotypic Diversity ◽  
Force Production ◽  
And Function ◽  
Muscle Contractile

The control of force production in vascular smooth muscle is critical to the normal regulation of blood flow and pressure, and altered regulation is common to diseases such as hypertension, heart failure, and ischemia. A great deal has been learned about imbalances in vasoconstrictor and vasodilator signals, e.g., angiotensin, endothelin, norepinephrine, and nitric oxide, that regulate vascular tone in normal and disease contexts. In contrast there has been limited study of how the phenotypic state of the vascular smooth muscle cell may influence the contractile response to these signaling pathways dependent upon the developmental, tissue-specific (vascular bed) or disease context. Smooth, skeletal, and cardiac muscle lineages are traditionally classified into fast or slow sublineages based on rates of contraction and relaxation, recognizing that this simple dichotomy vastly underrepresents muscle phenotypic diversity. A great deal has been learned about developmental specification of the striated muscle sublineages and their phenotypic interconversions in the mature animal under the control of mechanical load, neural input, and hormones. In contrast there has been relatively limited study of smooth muscle contractile phenotypic diversity. This is surprising given the number of diseases in which smooth muscle contractile dysfunction plays a key role. This review focuses on smooth muscle contractile phenotypic diversity in the vascular system, how it is generated, and how it may determine vascular function in developmental and disease contexts.

scholarly journals Excessive adventitial stress drives inflammation-mediated fibrosis in hypertensive aortic remodelling in mice

2021 ◽  
Vol 18 (180) ◽  
pp. 20210336
Author(s):  
Bart Spronck ◽  
Marcos Latorre ◽  
Mo Wang ◽  
Sameet Mehta ◽  
Alexander W. Caulk ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Wall Stress ◽  
Inflammatory Cells ◽  
Elevated Blood ◽  
Functional Studies ◽  
Matrix Deposition ◽  
Biomechanical Models ◽  
Before And After ◽  
Muscle Contractile ◽  
Increased Pressure

Hypertension induces significant aortic remodelling, often adaptive but sometimes not. To identify immuno-mechanical mechanisms responsible for differential remodelling, we studied thoracic aortas from 129S6/SvEvTac and C57BL/6 J mice before and after continuous 14-day angiotensin II infusion, which elevated blood pressure similarly in both strains. Histological and biomechanical assessments of excised vessels were similar at baseline, suggesting a common homeostatic set-point for mean wall stress. Histology further revealed near mechano-adaptive remodelling of the hypertensive 129S6/SvEvTac aortas, but a grossly maladaptive remodelling of C57BL/6 J aortas. Bulk RNA sequencing suggested that increased smooth muscle contractile processes promoted mechano-adaptation of 129S6/SvEvTac aortas while immune processes prevented adaptation of C57BL/6 J aortas. Functional studies confirmed an increased vasoconstrictive capacity of the former while immunohistochemistry demonstrated marked increases in inflammatory cells in the latter. We then used multiple computational biomechanical models to test the hypothesis that excessive adventitial wall stress correlates with inflammatory cell infiltration. These models consistently predicted that increased vasoconstriction against an increased pressure coupled with modest deposition of new matrix thickens the wall appropriately, restoring wall stress towards homeostatic consistent with adaptive remodelling. By contrast, insufficient vasoconstriction permits high wall stresses and exuberant inflammation-driven matrix deposition, especially in the adventitia, reflecting compromised homeostasis and gross maladaptation.

The influence of osteopathic correction on the rate of various rhythms of the body

2019 ◽  
pp. 64-71 ◽  
Author(s):  
A. E. Chernikova ◽  
Yu. P. Potekhina
Keyword(s):  
Heart Rate ◽  
Respiratory Rate ◽  
Age Groups ◽  
Biomechanical Properties ◽  
Dispersion Analysis ◽  
The Body ◽  
Body Tissues ◽  
Age Related ◽  
Significant Difference ◽  
Before And After

Introduction. An osteopathic examination determines the rate, the amplitude and the strength of the main rhythms (cardiac, respiratory and cranial). However, there are relatively few studies in the available literature dedicated to the influence of osteopathic correction (OC) on the characteristics of these rhythms.Goal of research — to study the influence of OC on the rate characteristics of various rhythms of the human body.Materials and methods. 88 adult osteopathic patients aged from 18 to 81 years were examined, among them 30 men and 58 women. All patients received general osteopathic examination. The rate of the cranial rhythm (RCR), respiratory rate (RR) heart rate (HR), the mobility of the nervous processes (MNP) and the connective tissue mobility (CTM) were assessed before and after the OC session.Results. Since age varied greatly in the examined group, a correlation analysis of age-related changes of the assessed rhythms was carried out. Only the CTM correlated with age (r=–0,28; p<0,05) in a statistically significant way. The rank dispersion analysis of Kruskal–Wallis also showed statistically significant difference in this indicator in different age groups (p=0,043). With the increase of years, the CTM decreases gradually. After the OC, the CTM, increased in a statistically significant way (p<0,0001). The RCR varied from 5 to 12 cycles/min in the examined group, which corresponded to the norm. After the OC, the RCR has increased in a statistically significant way (p<0,0001), the MNP has also increased (p<0,0001). The initial heart rate in the subjects varied from 56 to 94 beats/min, and in 15 % it exceeded the norm. After the OC the heart rate corresponded to the norm in all patients. The heart rate and the respiratory rate significantly decreased after the OC (р<0,0001).Conclusion. The described biorhythm changes after the OC session may be indicative of the improvement of the nervous regulation, of the normalization of the autonomic balance, of the improvement of the biomechanical properties of body tissues and of the increase of their mobility. The assessed parameters can be measured quickly without any additional equipment and can be used in order to study the results of the OC.

EFEITOS DO DEEP RUNNING SOBRE A AMPLITUDE DE MOVIMENTO E A CAPACIDADE FUNCIONAL DOS MEMBROS SUPERIORES DE MULHERES MASTECTOMIZADAS: RELATO DE CASOS

2019 ◽  
pp. 121-131
Keyword(s):  
Range Of Motion ◽  
Upper Limb ◽  
Functional Capacity ◽  
External Rotation ◽  
Treatment Protocol ◽  
Range Of Movement ◽  
Flexion Extension ◽  
Before And After ◽  
In The Beginning ◽  
And Function

Introduction: Breast cancer is the most common type of cancer among women in Brazil and in the worl. The surgical treatment procedure may cause severe morbidity in the upper limb homolateral to surgery, including the reduction of the range of motion, with consequent impairment of function. A physiotherapeutic approach has an important role in the recover range of motion and the functionality of these women, guaranteeing the occupational, domestestic, familiar and conjugated activities, and, in this way, also improving the quality of life. Objectives: To analyse chances in the shoulder's range of motion and the functional capacity of the upper limbs, promoted by the deep running procedure in women with late postoperative mastectomy. Methods: All the patients were submitted to an evaluation in the beginning and end of the treatment, including: goniometry of flexion, extension, abduction, adduction, internal and external rotation of the shoulder joint; and function capacity analysis in activities that involve the upper members by DASH questionnaire. The treatment protocol includes twelve sessions of deep running, realized twice a week, in deep pool, for 20-minute during six weeks. Results: Were submitted to treatment a total of 4 patients. Despite the improvement in the numerical values, statistically significant differences were not found on the range of movements and in the functional capacity of upper members before and after the deep running sessions in post-mastectomy women. Conclusion: Deep running had effects on the numerical values of range of movement and upper limb functionality in women in the late postoperative period of the mastectomy procedure, but without statistically significant differences.

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