Flexural pulse wave velocity in blood vessels.

Arteriosclerosis is a major risk factor for cardiovascular disease and results in arterial vessel stiffening. Velocity estimation of the pulse wave sent by the heart and propagating into the arteries is a widely accepted biomarker. This symmetrical pulse wave propagates at a speed which is related to the Young's modulus through the Moens Korteweg (MK) equation. Recently, an antisymmetric flexural wave has been observed in vivo. Unlike the symmetrical wave, it is highly dispersive. This property offers promising applications for monitoring arterial stiffness and early detection of atheromatous plaque. However, as far as it is known, no equivalent of the MK equation exists for flexural pulse waves. To bridge this gap, a beam based theory was developed, and approximate analytical solutions were reached. An experiment in soft polymer artery phantoms was built to observe the dispersion of flexural waves. A good agreement was found between the analytical expression derived from beam theory and experiments. Moreover, numerical simulations validated wave speed dependence on the elastic and geometric parameters at low frequencies. Clinical applications, such as arterial age estimation and arterial pressure measurement, are foreseen.

Analysis of effects of acute hypovolemia on arterial stiffness in rabbits monitored with cardio-ankle vascular index.

Although elasticity of the conduit arteries is known to be contribute effective peripheral circulation via Windkessel effects, the relationship between changes in intra-aortic blood volume and conduit artery elasticity remains unknown. Here we assessed the effects of change in intra-aortic blood volume induced by blood removal and subsequent blood transfusion on arterial stiffness and the involvement of autonomic nervous activity using our established rabbit model in the presence or absence of the ganglion blocker hexamethonium (100 mg/kg). Blood removal at a rate of 1 mL/min gradually decreased the blood pressure and blood flow of the common carotid artery but increased a stiffness indicator the cardio-ankle vascular index, which was equally observed in the presence of hexamethonium. These results suggest that arterial stiffness acutely responds to changes in intra-aortic blood volume independent of autonomic nervous system modification.

TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.

Cardiovascular calcification (CVC) is associated with increased morbidity and mortality. It develops in several diseases and locations, such as in the tunica intima in atherosclerosis plaques, in the tunica media in type 2 diabetes and chronic kidney disease, and in aortic valves. In spite of the wide occurrence of CVC and its detrimental effects on cardiovascular diseases (CVD), no treatment is yet available. Most of CVC involve mechanisms similar to those occurring during endochondral and/or intramembranous ossification. Logically, since tissue-nonspecific alkaline phosphatase (TNAP) is the key-enzyme responsible for skeletal/dental mineralization, it is a promising target to limit CVC. Tools have recently been developed to inhibit its activity and preclinical studies conducted in animal models of vascular calcification already provided promising results. Nevertheless, as its name indicates, TNAP is ubiquitous and recent data indicate that it dephosphorylates different substrates in vivo to participate in other important physiological functions besides mineralization. For instance, TNAP is involved in the metabolism of pyridoxal phosphate and the production of neurotransmitters. TNAP has also been described as an anti-inflammatory enzyme able to dephosphorylate adenosine nucleotides and lipopolysaccharide. A better understanding of the full spectrum of TNAP's functions is needed to better characterize the effects of TNAP inhibition in diseases associated with CVC. In this review, after a brief description of the different types of CVC, we describe the newly uncovered additional functions of TNAP and discuss the expected consequences of its systemic inhibition in vivo.

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

Numerical simulation of the transport of nanoparticles as drug carriers in hydromagnetic blood flow through a diseased artery with vessel wall permeability and rheological effects.

The present study considers the mathematical modeling of unsteady non-Newtonian hydro-magnetic nano-hemodynamics through a rigid cylindrical artery featuring two different stenoses (composite and irregular). The Ostwald-De Waele power-law fluid model is adopted to simulate the non-Newtonian characteristics of blood. Inspired by drug delivery applications for cardiovascular treatments, blood is considered doped with a homogenous suspension of biocompatible nanoparticles. The arterial vessel exhibits the permeability effect (lateral influx/efflux), and an external magnetic field is also applied in the radial direction to the flow. A combination of the Buongiorno and Tiwari-Das nanoscale models is adopted. The strongly nonlinear nature of the governing equations requires a robust numerical method, and therefore the finite difference technique is deployed to solve the resulting equations. Validation of solutions for the pure blood case (absence of nanoparticles) is included. Comprehensive solutions are presented for shear-thickening (n = 1.5) and shear-thinning (n = 0.5) blood flow for the effects of crucial nanoscale thermophysical, solutal parameters, and hydrodynamic parameters. Comparison of profiles (velocity, temperature, wall shear stress, and flow rate) is also made for composite and irregular stenosis. Colour visualization of streamline plots is included for pure blood and nano mediated blood both with and without applied magnetic field. The inclusion of nanoparticles (Cu/blood) within blood increases the axial velocity of blood. By applying external magnetic field in the radial direction, axial velocity is significantly damped whereas much less dramatic alterations are computed in blood temperature and concentration profiles. The simulations are relevant to the diffusion of nano-drugs in magnetic targeted treatment of stenosed arterial diseases.

Microstructural Characterization of Resistance Artery Remodelling in Diabetes Mellitus.

INTRODUCTION: Microvascular remodelling is a symptom of cardiovascular disease. Despite the mechanical environment being recognized as a major contributor to the remodelling process, it is currently only understood in a rudimentary way. OBJECTIVE: A morphological and mechanical evaluation of the resistance vasculature in health and diabetes mellitus. METHODS: The cells and extracellular matrix of human subcutaneous resistance arteries from abdominal fat biopsies were imaged using two-photon fluorescence and second harmonic generation at varying transmural pressure. The results informed a two-layer mechanical model. RESULTS: Diabetic resistance arteries reduced in wall area as pressure was increased. This was attributed to the presence of thick, straight collagen fibre bundles that braced the outer wall. The abnormal mechanical environment caused the internal elastic lamina and endothelial and vascular smooth muscle cell arrangements to twist. CONCLUSIONS: Our results suggest diabetic microvascular remodelling is likely to be stress-driven, comprising at least 2 stages: (1) Laying down of adventitial bracing fibres that limit outward distension, and (2) Deposition of additional collagen in the media, likely due to the significantly altered mechanical environment. This work represents a step towards elucidating the local stress environment of cells, which is crucial to build accurate models of mechanotransduction in disease.

The role of atherectomy in BTK lesions: a systematic review.

INTRODUCTION: The aim of this paper was to evaluate the current role of atherectomy techniques (ATH) in treatment of peripheral arterial disease (PAD) at below the knee (BTK) arteries. EVIDENCE ACQUISITION: The PubMed and Embase were searched (last search on 11 September 2021) for studies reporting on the early and mid-term outcomes of ATH in BTK vessels. Analysis included the data from six studies, with a total of 1062 PAD patients treated with various ATH techniques. We compared them the ATH outcomes with the contemporaneous outcomes of plain balloon angioplasty alone or with bailout stenting. Early safety and efficacy were accessed with perioperative and 30-day technical success (TS) rate, which included the primary patency of the treated BTK arterial segment. Evaluation of clinical performance was based on target limb revascularization (TLR) and on major limb adverse events (MALEs) rates. EVIDENCE SYNTHESIS: The current body of literature mainly includes retrospective observational studies, and the level of derived evidence is low. The mean perioperative and 30-day TS rate was 87.3%. The mean reported TLR and MALEs rates at 12 months were 6.6% and 4.7% respectively. The relevant rates in studies reporting at 24 months were 24.3% and 31.7% while in studies reporting at 36 months the rates were 37.0% and 23.0% respectively. CONCLUSIONS: Based in low-quality evidence, it seems that ATH in BTK vessels has a high safety, high efficacy profile and durable outcomes at 12 months. In the mid-term, the clinical success of ATH is compromised by increased TLR and MALEs rates. Comparison of ATH with other endovascular techniques in BTK treatment of PAD shows a slight lead of ATH at 1-year and equivalent clinical performance in the mid-term. Overall, ATH has a significant and potentially predominant role in treatment of BTK vessels.

Vasodilator Dysfunction in Human Obesity: Established and Emerging Mechanisms.

ABSTRACT: Human obesity is associated with insulin resistance and often results in a number of metabolic abnormalities and cardiovascular complications. Over the past decades, substantial advances in the understanding of the cellular and molecular pathophysiological pathways underlying the obesity-related vascular dysfunction have facilitated better identification of several players participating in this abnormality. However, the complex interplay between the disparate mechanisms involved has not yet been fully elucidated. Moreover, in medical practice, the clinical syndromes stemming from obesity-related vascular dysfunction still carry a substantial burden of morbidity and mortality; thus, early identification and personalized clinical management seem of the essence. Here, we will initially describe the alterations of intravascular homeostatic mechanisms occurring in arteries of obese patients. Then, we will briefly enumerate those recognized causative factors of obesity-related vasodilator dysfunction, such as vascular insulin resistance, lipotoxicity, visceral adipose tissue expansion, and perivascular adipose tissue abnormalities; next, we will discuss in greater detail some emerging pathophysiological mechanisms, including skeletal muscle inflammation, signals from gut microbiome, and the role of extracellular vesicles and microRNAs. Finally, it will touch on some gaps in knowledge, as well as some current acquisitions for specific treatment regimens, such as glucagon-like peptide-1 enhancers and sodium-glucose transporter2 inhibitors, that could arrest or slow the progression of this abnormality full of unwanted consequences.

RNO3 QTL regulates vascular structure and arterial stiffness in the spontaneously hypertensive rat.

Increased arterial stiffness is an independent risk factor for hypertension, stroke, and cardiovascular morbidity. Thus, understanding the factors contributing to vascular stiffness is of critical importance. Here, we used a rat model containing a known quantitative trait locus (QTL) on chromosome 3 (RNO3) for vasoreactivity to assess potential genetic elements contributing to blood pressure, arterial stiffness, and their downstream effects on cardiac structure and function. Although no differences were found in blood pressure at any time point between parental spontaneously hypertensive rats (SHRs) and congenic SHR.BN3 rats, the SHRs showed a significant increase in arterial stiffness measured by pulse wave velocity. The degree of arterial stiffness increased with age in the SHRs and was associated with compensatory cardiac changes at 16 wk of age, and decompensatory changes at 32 wk, with no change in cardiac structure or function in the SHR.BN3 hearts at these time points. To evaluate the arterial wall structure, we used multiphoton microscopy to quantify cells and collagen content within the adventitia and media of SHR and SHR.BN3 arteries. No difference in cell numbers or proliferation rates was found, although phenotypic diversity was characterized in vascular smooth muscle cells. Herein, significant anatomical and physiological differences related to arterial structure and cardiovascular tone including collagen, pulse wave velocity (PWV), left ventricular (LV) geometry and function, and vascular smooth muscle cell (VSMC) contractile apparatus proteins were associated with the RNO3 QTL, thus providing a novel platform for studying arterial stiffness. Future studies delimiting the RNO3 QTL could aid in identifying genetic elements responsible for arterial structure and function.

Ageing-induced hypercontractility is related to functional enhancement of STIM/Orai and upregulation of Orai 3 in rat and human penile tissue.

The role of STIM/Orai calcium entry system on vascular ageing has not been elucidated. We aimed to evaluate the influence of ageing on STIM/Orai signalling and its role on ageing-induced alterations of contractile function in rat corpus cavernosum (RCC) and human penile resistance arteries (HPRA) and corpus cavernosum (HCC). RCC was obtained from 3 months-old and 20 months-old animals. HPRA and HCC were obtained from organ donors of varied ages without history of erectile dysfunction. Aging was associated with enhanced norepinephrine (NE)- and thromboxane analogue (U46619)-induced contractions in RCC which were significantly inhibited by the STIM/Orai inhibitor, YM-58483 (20 µM). Other STIM/Orai inhibitor, 2-aminoethyldiphenylborate also reduced NE-induced contractions in RCC from aged rats. YM-58483 significantly reduced neurogenic contractions and potentiated neurogenic relaxations in RCC from aged rats. In HCC and HPRA, NE-induced contractions were significantly enhanced in older subjects (>65 years-old) but YM-58483 completely reversed ageing-related hypercontractility. Ageing did not modify STIM-1 and Orai1 protein expressions but Orai3 was significantly overexpressed in cavernosal tissue from old rats and older subjects. Contribution of STIM/Orai to cavernosal contraction increases with ageing together with increased expression of Orai3. Orai inhibition could be a potential therapeutic strategy to reduce ageing-related impact on vascular/erectile function.

Molecular Interactions of Arterial Hypertension in Its Target Organs.

Arterial hypertension (AH) is a major risk factor for the development of cardiovascular diseases. It is estimated that the disease affects between 10% and 20% of the adult population and is responsible for 5.8% of all deaths worldwide. Several pathophysiologic factors are crucial in AH, including inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress and inflammation. The heart, kidney, brain, retina and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled and untreated AH accelerates the damage to these organs and could cause their failure. Damage to these organs could also manifest as coronary heart disease, cognitive impairment, retinopathy or optic neuropathy. For better understanding, it is important to analyze molecular factors which take part in pathogenesis of AH and hypertension-related target organ damage. In our paper, we would like to focus on molecular interactions of AH in the heart, blood vessels, brain and kidneys. We focus on matrix metalloproteinases, the role of immune system, the renin-angiotensin-aldosterone system and oxidative stress in hypertensive induced organ damage.

Roles of MicroRNAs in Peripheral Artery In-Stent Restenosis after Endovascular Treatment.

Endovascular repair including percutaneous transluminal angioplasty (PTA) and stent implantation has become the standard approach for the treatment of peripheral arterial disease; however, restenosis is still the main limited complication for the long-term success of the endovascular repair. Endothelial denudation and regeneration, inflammatory response, and neointimal hyperplasia are major pathological processes occurring during in-stent restenosis (ISR). MicroRNAs exhibit great potential in regulating several vascular biological events in different cell types and have been identified as novel therapeutic targets as well as biomarkers for ISR prevention. This review summarized recent experimental and clinical studies on the role of miRNAs in ISR modification, with the aim of unraveling the underlying mechanism and potential therapeutic strategy of ISR.