Vascular Remodeling in Health and Disease

The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1, 2, 3, 4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as elevated shear stress or increased intravascular pressure, may eventually become maladaptive, leading to impaired vascular function. The vascular endothelium, owing to its location lining the lumen of blood vessels, plays a pivotal role in regulation of all aspects of vascular function and homeostasis.5 Thus, not surprisingly, endothelial dysfunction has been recognized as the harbinger of all major cardiovascular diseases such as hypertension, atherosclerosis, and diabetes.6, 7, 8 The endothelium elaborates a variety of substances that influence vascular tone and protect the vessel wall against inflammatory cell adhesion, thrombus formation, and vascular cell proliferation.8, 9, 10 Among the primary biologic mediators emanating from the endothelium is nitric oxide (NO) and the arachidonic acid metabolite prostacyclin [prostaglandin I2 (PGI2)], which exert powerful vasodilatory, antiadhesive, and antiproliferative effects in the vessel wall

How blind are they? Phototactic responses in stygobiont diving beetles (Coleoptera: Dytiscidae) from calcrete aquifers of Western Australia

Subterranean water beetles endemic to groundwater calcretes of Western Australia exhibit convergent traits typical of troglomorphic arthropods, including loss of eyes, pigmentation and wings. As these dytiscid species are estimated to have been isolated underground in permanent darkness for over three million years, it is predicted that they will completely lack phototactic responses. We tested this hypothesis by analysing the behaviour of six subterranean beetle species within an observational arena with dark and light hemispheres. Scan samples at 1 min intervals and total time spent on each hemisphere were recorded over a 20 min period, testing at least 15 individuals per species. We quantified behaviour as an index (dark ratio) so that individual species in this, and future, studies can be consistently compared. Results analysed as both categorical and absolute proportion of time spent in each hemisphere suggest negative phototaxis in Paroster macrosturtensis. The remaining five species did not display any preference for either light or dark hemispheres. These results raise the possibility that some ancestral Par oster species may have exhibited negative phototactic behaviour prior to subterranean colonization. The retention of such a behavioural trait in lightless environments could represent the maintenance for some unknown pleiotropic function. Alternatively, it is possible that insufficient time has passed for neutral processes to render photoreception genes and phototactic behaviours non-functional. Our study adds to a growing body of evidence that implies highly troglomorphic animals may have evolved from ancestral species that exhibited negative phototaxis as a preadaptation to living in permanent darkness.Barbara L Langille, Simon M Tierney, Andrew D Austin, William F Humphreys and Steven J B Coope

Complementary vasoactivity and matrix remodelling in arterial adaptations to altered flow and pressure

Arteries exhibit a remarkable ability to adapt to sustained alterations in biomechanical loading, probably via mechanisms that are similarly involved in many arterial pathologies and responses to treatment. Of particular note, diverse data suggest that cell and matrix turnover within vasoaltered states enables arteries to adapt to sustained changes in blood flow and pressure. The goal herein is to show explicitly how altered smooth muscle contractility and matrix growth and remodelling work together to adapt the geometry, structure, stiffness and function of a representative basilar artery. Towards this end, we employ a continuum theory of constrained mixtures to model evolving changes in the wall, which depend on both wall shear stress-induced changes in vasoactive molecules (which alter smooth muscle proliferation and synthesis of matrix) and intramural stress-induced changes in growth factors (which alter cell and matrix turnover). Simulations show, for example, that such considerations help explain the different rates of experimentally observed adaptations to increased versus decreased flows as well as differences in rates of change in response to increased flows or pressures

Evidence for speciation underground in diving beetles (Dytiscidae) from a subterranean archipelago

Most subterranean animals are assumed to have evolved from surface ancestors following colonisation of a cave system, however very few studies have raised the possibility of 'subterranean speciation' in underground habitats (i.e. obligate cave-dwelling organisms (troglobionts) descended from troglobiotic ancestors). Numerous endemic subterranean diving beetle species from spatially-discrete calcrete aquifers in Western Australia (stygobionts) have evolved independently from surface ancestors; however, several cases of sympatric sister species raises the possibility of subterranean speciation. We tested this hypothesis using vision (phototransduction) genes that are evolving under neutral processes in subterranean species and purifying selection in surface species. Using sequence data from 32 subterranean and five surface species in the genus Paroster (Dytiscidae), we identified deleterious mutations in: long wavelength opsin (lwop), arrestin 1 (arr1), and arrestin 2 (arr2) shared by a sympatric sister-species triplet, arr1 shared by a sympatric sister-species pair, and lwop and arr2 shared among closely related species in adjacent calcrete aquifers. In all cases, a common ancestor possessed the function-altering mutations, implying they were already adapted to aphotic environments. Our study represents one of the first confirmed cases of subterranean speciation in cave insects. The assessment of genes undergoing pseudogenisation provides a novel way of testing modes of speciation and the history of diversification in blind cave animals. This article is protected by copyright. All rights reserved.Barbara L. Langille ... Danielle N. Stringer, Simon M. Tierney, William F. Humphreys, Andrew D. Austin, Steven J. B. Cooper ... et al

Parallel decay of vision genes in subterranean water beetles

In the framework of neutral theory of molecular evolution, genes specific to the development and function of eyes in subterranean animals living in permanent darkness are expected to evolve by relaxed selection, ulti- mately becoming pseudogenes. However, definitive empirical evidence for the role of neutral processes in the loss of vision over evolutionary time remains controversial. In previous studies, we characterized an assemblage of independently-evolved water beetle (Dytiscidae) species from a subterranean archipelago in Western Australia, where parallel vision and eye loss have occurred. Using a combination of transcriptomics and exon capture, we present evidence of parallel coding sequence decay, resulting from the accumulation of frameshift mutations and premature stop codons, in eight phototransduction genes (arrestins, opsins, ninaC and transient receptor potential channel genes) in 32 subterranean species in contrast to surface species, where these genes have open reading frames. Our results provide strong evidence to support neutral evolutionary processes as a major contributing factor to the loss of phototransduction genes in subterranean animals, with the ultimate fate being the irreversible loss of a light detection system.Barbara L. Langille, Simon M. Tierney, Terry Bertozzi, Perry G. Beasley-Hall, Tessa M. Bradford, Erinn P. Fagan-Jeffries, Josephine Hyde, Remko Leijs, Matthew Richardson, Kathleen M. Saint, Danielle N. Stringer, Adrian Villastrigo, William F. Humphreys, Andrew D. Austin, Steven J.B. Coope

An in Vitro Device for Evaluation of Cellular Response to Flows Found At the Apex of Arterial Bifurcations

Intracranial aneurysms (ICA) are abnormal dilations of the cerebral arteries, most commonly located at the apices of bifurcations. The ability of the arterial wall, particularly the endothelial cells forming the inner lining of the wall, to respond appropriately to hemodynamic stresses is critical to arterial health. ICA initiation is believed to be caused by a breakdown in this homeostatic mechanism leading to wall degradation. Due to the complex nature of this process, there is a need for both controlled in vitro and in vivo studies. Chung et al. developed an in vitro chamber for analyzing the response of biological cells to the hemodynamic wall shear stress fields generated by the impinging flows found at arterial bifurcations [6, 7]. Here, we build on this work and design an in vitro flow chamber that can be used to reproduce specific magnitudes of wall shear stress (WSS) and gradients of wall shear stress. Particular attention is given to reproducing spatial distributions of these functions that have been shown to induce pre-aneurysmal changes in vivo [38]. We introduce a measure of the gradient of the wall shear stress vector (WSSVG) which is appropriate for complex 3D flows and reduces to expected measures in simple 2D flows. The WSSVG is a scalar invariant and is therefore appropriate for use in constitutive equations for vessel remodeling in response to hemodynamic loads [34, 35]