Journal of Vascular Diseases

The development of new organic nitrates is still relevant due to the clinical limitations of their use. Tetrahydrofurfuryl nitrate (NTHF) is a new organic nitrate obtained through a synthetic route of sugarcane. The aim of this research was to investigate the cardiovascular effects promoted by NTHF in rats. Isolated vascular smooth muscle cells (VSMC) were incubated with a specific probe and were analyzed in a flow cytometer to measure the NO concentration after NTHF treatment. Rat superior mesenteric rings were isolated and used for isometric tension recordings and the evaluation of the vasorelaxant activity induced by NTHF. For the in vivo study, polyethylene catheters were implanted into the abdominal aorta and inferior vena cava of the rats (weighing 250–300 g). NTHF increased NO levels in rat VSMCs. In anesthetized rats, NTHF induced hypotension and bradycardia after intravenous administration. These effects were attenuated after the administration of a sGC inhibitor, methylene blue. In the phenylephrine pre-contracted superior mesenteric artery of rats, NTHF (1 pM–10 μM) induced concentration-dependent vasodilatation in both the intact and removed endothelium. Furthermore, in the presence of NO° scavenging (C-PTIO and HDX) or ODQ, a sGC inhibitor, the vasorelaxation induced by NTHF was decreased. NTHF tolerance was evaluated in mesenteric artery rings previously exposed with isolated concentrations of the new organic nitrate. The vasorelaxant effect was not modified by exposure to nitrate. These results demonstrated that NTHF induced hypotension and bradycardia in vivo and a vasorelaxant effect with the participation of the NO-sGC-PKG pathway and triggering calcium-activated K⁺ channels without vascular tolerance induction. Full article

The microvessel neurovascular unit, with its brain endothelial cells (BEC) and blood–brain barrier remodeling, is important in the development of impaired cognition in sporadic or late-onset Alzheimer’s disease (LOAD), which is associated with aging and is highly prevalent in older populations (≥65 years of age). It is also linked with vascular dementia and vascular contributions to cognitive impairment and dementia, including cerebral amyloid angiopathy in neurodegeneration. LOAD is considered to be the number one cause of dementia globally; however, when one considers the role of mixed dementia (MD)—the combination of both the amyloid cascade hypothesis and the vascular hypothesis of LOAD—it becomes apparent that MD is the number one cause. Microvessel BECs are the first cells in the brain to be exposed to peripheral neurotoxins from the systemic circulation and are therefore the brain cells at the highest risk for early and chronic injury. Therefore, these cells are the first to undergo injury, followed by excessive and recurrent wound healing and remodeling processes in aging and other age-related diseases such as cerebrocardiovascular disease, hypertension, type 2 diabetes mellitus, and Parkinson’s disease. This narrative review explores the intricate relationship between microvessel remodeling, cerebral small vessel disease (SVD), and neurodegeneration in LOAD. It also discusses the current understanding of how microvessel dysfunction, disruption, and pathology contribute to the pathogenesis of LOAD and highlights potential avenues for therapeutic intervention. Full article

Background and Purpose: The cerebral circulation is highly regulated to maintain brain perfusion, keeping an equilibrium between the brain tissue, cerebrospinal fluid (CSF) and blood of the arterial and venous systems. Cerebral venous drainage abnormalities have been implicated in multiple cerebrovascular diseases. The purpose of this study is to evaluate the relationship between the arterial inflow (AI) and the cerebral venous outflow (CVO) and their correlation with the cardiac outflow in healthy adults and children to understand the role of the emissary veins in normal venous drainage. Materials and Methods: A total of 31 healthy volunteers (24 adults (39.5 ± 16.0) and seven children (3.4 ± 2.2)) underwent intracranial 4D flow with full circle of Willis coverage and 2D PC-MRI at the level of the transverse sinus for measurement of the AI and CVO, respectively. The AI was calculated as the sum of the flow values in the bilateral internal carotid and basilar arteries. The CVO was calculated as the sum of the flow values in the bilateral transverse sinuses. The cardiac outflow was measured via 2D PC-MRI with retrospective ECG gating with images acquired at the proximal ascending aorta (AAo) and descending (DAo) aorta. The ratios of the AI/AAo flow and CVO/AI were calculated to characterize the fraction of cerebral arterial inflow in relation to cardiac outflow and venous blood draining through the transverse sinuses, respectively. Results: The AI and CVO were significantly correlated (r = 0.81, p < 0.001). The CVO constituted approximately 60–70% of the AI. The CVO/AI ratio was significantly lower in children versus adults (p = 0.025). In adults, the negative correlation of the AI with age remained strong (r = −0.81, p < 0.001). However, the CVO was not significantly associated with age. Conclusion: The CVO/AI ratio suggests an important role of the emissary veins, accounting for approximately 30–40% of venous drainage. The lower CVO/AI ratio in children, although partially related to decreased AI with age, suggests a greater role of the emissary veins in childhood, which strongly decreases with age. Full article

Background/Objectives: Head and neck free-flap reconstructions are often required to treat tumors or extensive post-traumatic jaw defects. The facial artery is the standard receiving vessel for intraoral microvascular anastomoses. However, its use is associated with several disadvantages, such as lesions of buccal nerve branches of the facial nerve or the parotid duct, as well as variability in course and diameter. The aim of this study is to investigate whether branches of the sublingual artery can be considered as an alternative intraoral supply vessel to the facial artery to avoid these drawbacks. Methods: Twelve formalin-fixed cadaveric heads with 24 sides (n = 24) were dissected. The origin, course, branching pattern, and distribution of the sublingual artery were examined. In addition, the diameters of the branches of the sublingual artery were assessed to identify potential supply vessels for anastomoses. Results: In ten of the twenty-four cases (41.7%), the sublingual artery originated from the lingual artery, and in nine cases (37.5%), the lingual artery originated from the facial artery. The main trunk of the sublingual artery was present in the floor of the mouth in all cases (100%), with a diameter of ≥0.9 mm in vitro (1 mm in vivo). In 15 of the 24 half heads (62.5%), branches of the sublingual artery with ≥0.9 mm were identified in this space, with the main branch being considerably stronger. Conclusions: The large diameter of the sublingual artery in the floor of the mandible suggests that this vessel or its branches could be considered as alternative pedicles for intraoral anastomoses in mandibular microvascular free-flap grafts. Full article

The perivascular adipose tissue (PVAT) regulates the arterial tone by releasing vasoactive molecules. PVAT dysfunction favoring the vasorelaxation response could contribute to the development of kidney disease in metabolic syndrome (MetS). Previously, we demonstrated that overactivation of angiotensin II signaling in the PVAT deteriorates the compensatory PVAT effects in rats with MetS (SHRSP.Z-Lepr^fa/IzmDmcr (SPZF) and SHR/NDmcr-cp (CP) rats). Apelin is an endogenous regulator of angiotensin II. Therefore, we investigated whether changes in apelin levels in the PVAT alter PVAT function and impair kidney function in MetS. Twenty-three-week-old male and female SPZF and CP rats were used. In the female CP rats, apelin mRNA levels in renal arterial PVAT, enhancing effects of the PVAT on acetylcholine-induced relaxation in renal arteries, and estimated glomerular filtration rate (eGFR) were the highest, and urine protein levels and homeostasis model assessment of insulin resistance (HOMA-IR) were the lowest. Apelin mRNA levels were positively correlated with the enhancing effects of the PVAT on vasorelaxation and eGFR but negatively correlated with urine protein levels and HOMA-IR. Moreover, apelin levels positively correlated with mRNA levels of angiotensin-converting enzyme 2 and angiotensin II type 1 receptor-associated protein, which are negative regulators of angiotensin II. This study suggests that a decline in apelin levels in the PVAT, probably owing to angiotensin II, is associated with PVAT dysfunction on vascular tone, resulting in impaired kidney function in MetS. Full article

Purpose: This study investigated the impact of two different resistance training (RT) protocols on cardiac autonomic modulation during exercise recovery in trained individuals. It was hypothesized that a hypertrophic resistance training program would induce more significant stress and negatively affect cardiac autonomic modulation compared to a power/force resistance training program. Methods: Six healthy, trained participants (aged 18–40) were randomized in a crossover and controlled pilot study. Participants performed two RT protocols: (i) three sets of 10 repetitions with 85% of 10 RM, 60 s inter-set rest (3x10_60s) and (ii) eight sets of three repetitions with 85% of 3 RM, 120 s inter-set rest (8x3_120s). Heart rate variability (HRV) was measured before and 30 min after each RT session. Results: Significant reductions in HRV parameters (RMSSD, HF, and SD1) were observed following the 3x10_60s protocol (hypertrophic design) compared to baseline. Conversely, the 8x3_120s (power/force design) protocol did not show significant changes in HRV parameters. A significant interaction effect for time and RT protocol was found for all HRV measures with more significant reductions observed after 3x10_60s compared to 8x3_120s. Conclusions: The hypertrophic RT session (3x10_60s) significantly reduced HRV parameters, suggesting higher physiological stress and potentially negative implications for cardiac autonomic recovery than the power/force RT session (8x3_120s). These findings highlight the importance of considering exercise intensity and protocol design to manage cardiac autonomic stress during resistance training. Full article

Shear stress is one of the major hemodynamic forces acting on the endothelium. However, it is not well known how endothelial cells (EC) respond mechanically to these stimuli in vivo. Here we investigated whether changes in biomechanics properties and shear stress could increase cell susceptibility to injury, contributing to vascular fragility. We surgically implanted a shear stress modifier device on the carotid artery of ApoE-knockout mice (ApoE^−/−), which, due to its shape, causes a gradual stenosis in the vessel, resulting in distinct shear stress patterns. Our data show actin fibers accumulation in areas with higher lipid deposition in ApoE^−/−, indicating that dyslipidemia might interfere with EC actin cytoskeleton organization. We also showed that both shear stress and dyslipidemia were important for EC susceptibility to injury. Furthermore, lysosomal distribution, an important organelle for plasma membrane repair, was altered in ApoE^−/−, which could compromise EC’s ability to repair from damage. Therefore, dyslipidemia and variations in shear stress patterns not only affect cellular mechanics by compromising the actin cytoskeleton organization, but also enhance cell susceptibility to injury and alter vesicle trafficking in vascular cells. This may likely contribute to vascular fragility and thus to the initial steps of atherosclerosis development. Full article

The term “Transgender” is used to describe individuals whose gender identity is different from their external sexual anatomy at birth. The number of people identifying as transgender has increased in recent years, and consequently, the number of gender affirmation surgeries and the use of hormonal therapies has also increased. A wide range of hormonal therapies has emerged considering the target population, age, and final outcomes, and as such these are becoming increasingly developed and complex in order to be the most appropriate for each individual. However, the side effects of these therapies remain to be fully understood. Therefore, this review aims to assess the impact of hormone therapy, in both transgender men and women of different ages, on the lipid profile. From the studies analyzed, it is possible to conclude that there is a relationship between hormone therapy and the lipid profile, with different outcomes between transgender men and women. There is a reduction in cardiovascular risk for transgender women as opposed to transgender men, in whom cardiovascular risk seems to increase due to lipid changes. It is now necessary to understand the mechanisms involved in order to reduce the consequences of these therapies and promote positive health outcomes. Full article

Aging is a complex process inherent to and inevitable in humans. With life expectancy rising, there are concerns about the senior population’s wellbeing, and a hope of preventing certain diseases such as cardiovascular diseases. To achieve it, this study resorts to the implementation of an interventional program based on the comprehensive geriatric assessment model [AGA@4life]. The aim is to evaluate the effect of a new nutritional and exercise regime and evaluate possible changes in nitric oxide (NO) metabolites and endothelin 1 (ET-1). An intervention study was developed with 17 participants with ages of 65 and above. They were evaluated in the beginning [T0] and after eight weeks [T1], where NO metabolites and ET-1 levels were determined by enzymatic assays and the slot blot technique, respectively. There was a significant decrease in ET-1 levels in both the control (p < 0.001) and intervention (p = 0.04) groups from T0 to T1, but there was only a tendency for a decrease in the NO metabolite’s levels in the same conditions [p > 0.05]. Even though the NO metabolite levels did not increase as expected, possibly because of an increase in oxidative stress, the ET-1 levels decreased as expected and the overall results are promising, proving this program could have a beneficial effect on the geriatric population. Full article

Traumatic brain injury (TBI) results from external biomechanical forces that cause structural and physiological disturbances in the brain, leading to neuronal, axonal, and vascular damage. TBIs are predominantly mild (65%), with moderate (10%) and severe (25%) cases also prevalent. TBI significantly impacts health, increasing the risk of neurodegenerative diseases such as dementia, post injury. The initial phase of TBI involves acute disruption of the blood–brain barrier (BBB) due to vascular shear stress, leading to ischemic damage and amyloid-beta accumulation. Among the acute cerebrovascular changes after trauma are early progressive hemorrhage, micro bleeding, coagulopathy, neurovascular unit (NVU) uncoupling, changes in the BBB, changes in cerebral blood flow (CBF), and cerebral edema. The secondary phase is characterized by metabolic dysregulation and inflammation, mediated by oxidative stress and reactive oxygen species (ROS), which contribute to further neurodegeneration. The cerebrovascular changes and neuroinflammation include excitotoxicity from elevated extracellular glutamate levels, coagulopathy, NVU, immune responses, and chronic vascular changes after TBI result in neurodegeneration. Severe TBI often leads to dysfunction in organs outside the brain, which can significantly impact patient care and outcomes. The vascular component of systemic inflammation after TBI includes immune dysregulation, hemodynamic dysfunction, coagulopathy, respiratory failure, and acute kidney injury. There are differences in how men and women acquire traumatic brain injuries, how their brains respond to these injuries at the cellular and molecular levels, and in their brain repair and recovery processes. Also, the patterns of cerebrovascular dysfunction and stroke vulnerability after TBI are different in males and females based on animal studies. Full article

This review analyzes the clinicopathological features, diagnostic challenges, and clinical outcomes of 60 intraoral angiosarcoma (InO-AS) and 20 intraoral Kaposi sarcoma (InO-KS) cases. These malignancies primarily affect adults, with mean ages of 52.3 years for InO-AS and 44 years for InO-KS, and are rare in children. Both show a male predilection, with InO-KS strongly linked to HIV infection. Metastatic InO-AS typically appears smaller and is located in the mandibular or maxillary gingiva. Most InO-KS cases occur in HIV-positive individuals, often in nodular form. Histological differentiation of InO-AS from poorly differentiated carcinoma and spindle cell carcinoma requires a comprehensive panel of immunohistochemical markers such as CK, CD31, and CD34, while HHV-8 antibody and CD34 help diagnose InO-KS. Treatment for InO-AS involves surgery with radiotherapy and/or chemotherapy, while InO-KS management may include antiretroviral therapy for AIDS patients. InO-AS is aggressive, with over half of patients dying from the disease, whereas InO-KS generally has a less severe course. Despite their rarity, both InO-AS and InO-KS behave similarly to their extraoral counterparts. A key limitation noted in this review is the inconsistent histopathological reporting of AS, particularly regarding histopathological grade, which complicates the assessment and comparison of treatment outcomes. Full article

Purpose: To compare the efficacy and safety of percutaneous mechanical debulking (PMD) using mechanical rotational atherectomy combined with paclitaxel drug-coated balloon (DCB) versus using paclitaxel DCB alone in the treatment of in-stent restenosis. Material and Methods: This is a multicentric retrospective observational study conducted over a period of 2 years from 2020 to 2022. The study included 49 patients presented with chronic limb-threatening ischemia (CLTI) associated with in-stent restenosis, either acute (<14 days), subacute (<3 months) or chronic (>3 months). The enrolled patients underwent endovascular revascularization using either PMD combined with paclitaxel DCB or paclitaxel DCB only. They were followed up for 6 months after the intervention clinically and by duplex evaluation. Results: The lesion length was about 14.2 mm in the group treated by PMD+ DCB and 9.3 mm in the group treated by DCB alone. The technical success rate was the same between the two groups. However, the follow-up after 6 months showed that patencies for PMD + DCB and DCB alone were 15 (68.2%) patients and 15 (55.6%) patients, respectively (significant p value = 0.028). Procedural-related complications for PMD + DCB are distal embolization (9%) of cases and no vessel perforation. Regarding the candidates who were treated by DCB alone, there were minor groin hematomas (11.1%), distal arterial thrombosis (11.1%) and contrast-induced nephropathy (CIN) (11.1%) cases. Conclusion: The endovascular management of in-stent restenosis using percutaneous mechanical debulking (PMD) in conjunction with paclitaxel drug-coated balloon (DCB) showed that PMD combined with DCB is a safe and effective modality for achieving recanalization. It gives a satisfactory outcome in terms of technical success, freedom from clinically driven target lesion revascularization rate (CD-TLR) and mortality. Despite these promising results, further research with a large enrolled population may be required to determine the cost/benefit. Full article

Background: Recently, the arterial velocity pulse index (AVI) and arterial pressure volume index (API) have been used to evaluate arterial stiffness and endothelial function. As arterial stiffness and endothelial injury are risk factors for coronary artery disease (CAD), these two indexes are therefore expected to predict and evaluate the future risk of CAD and cardiovascular events before clinical manifestations. Methods: A total of 90 consecutive patients with coronary angiography (CAG) were enrolled. After excluding normal patients and acute coronary syndrome patients, forty-seven patients with CAD and thirty-two patients with coronary atherosclerosis, and baseline characteristics data were collected. A multifunctional blood pressure monitoring device, AVE-1500 (Shisei Datum, Tokyo, Japan), was used to measure the AVI and API before CAG, and immediately and 2 h, 24 h, and 48 h after CAG and (or) PCI in all the selected participants. Results: After adjusting for various variables using stepwise multiple linear regression analyses, we found that the AVI in the CAD subjects was significantly higher than that in the coronary atherosclerosis subjects before CAG (p = 0.02), immediately after CAG/PCI (p = 0.01), and 48 h after CAG/PCI (p = 0.01), whereas the AVI decreased 24–48 h rather than immediately after CAG/PCI in the CAD group. Moreover, we also found that the API clearly changed in both groups during the periprocedural period of CAG (p = 0.01). Conclusions: In accordance with the results, we propose that the API and AVI may be useful for predicting the early stage of CAD and may be promising as indicators to assess the effect of early revascularization. Full article

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a new disease entity occurring in the pediatric population two to six weeks after coronavirus exposure due to a systemic arteritis. We investigated post-hospital-discharge arterial function at short- and mid-term intervals using pulse wave velocity. We assessed associations between arterial function, left ventricular diastolic and systolic function and left ventricular mass. Materials and methods: Retrospective data collection was carried out on 28 patients with MIS-C with at least two outpatient pediatric cardiology clinic visits post hospital admission. The patients underwent assessment of systemic arterial function and cardiac function. Data included pulse wave velocity between carotid and femoral arteries and echocardiographic assessment of left ventricular systolic function (shortening and ejection fraction, longitudinal strain), diastolic function and left ventricular mass. Results: Pulse wave velocity significantly decreased from visit 1 to visit 2 (5.29 ± 1.34 m/s vs. 4.51 ± 0.91 m/s, p = 0.009). Left ventricular mass significantly decreased from visit 1 to visit 2 (42 ± 9 g/m^2.7 vs. 38 ± 7 g/m^2.7, p = 0.02). There was a significant negative correlation between the pulse wave velocity and E/A mitral inflow (−0.41, p < 0.05). Conclusions: Children have elevated pulse wave velocity and left ventricular mass in the short-term relative to mid-term values after hospital discharge. These results suggest that MIS-C is associated with transient systemic arterial dysfunction, which, in turn, may play a role in cardiac changes. Full article

Atherosclerotic coronary artery disease is a significant global health threat, impacting millions annually. Over time, plaque buildup narrows the coronary arteries, reducing blood flow to the heart muscle and resulting in myocardial ischemia. Timely diagnosis and intervention are crucial for restoring the blood flow to the heart muscle and preventing myocardial infarction. Given the limited availability of screening and diagnostic tests, the early diagnosis of myocardial ischemia remains challenging. While cardiac troponin is considered the gold standard for detecting myocardial injury, its effectiveness in identifying myocardial ischemia is limited. Ischemia-modified albumin (IMA) is a modified albumin variant that serves as a sensitive and early marker for ischemia. Despite extensive research on diagnostic applications of IMA as a biomarker for ischemia, significant gaps remain in understanding its formation, sensitive and specific detection, and precise clinical utility. This review aims to address these gaps by compiling literature on IMA discussing the latest findings on structure and formation, and detection methods. Further research is required to enhance understanding of the structure and formation of IMA, aiming to develop novel detection techniques or improve existing ones. However, currently, available sophisticated methods are associated with higher expenses and require specialized equipment and qualified personnel. Full article

Background: Evidence has demonstrated that non-habitual exercise, such as eccentric exercise, can increase reactive oxygen species and induce endothelial dysfunction, which plays a central role in the development of cardiovascular disease. Polyphenol-rich foods, such as cocoa, have been widely investigated in vascular function due to their antioxidant effect. Aims: The goal of this study was to evaluate the impact of microencapsulated cocoa (MC) polyphenols in the flow-mediated dilation (FMD) response and forearm muscle oxygenation (StO₂) parameters after an eccentric exercise. Methods: Thirteen physically active adults were enrolled in a randomized, double-blind, and crossover study. FMD and StO₂ were evaluated before and after 24 h, 48 h, and 72 h of eccentric exercise and MC or placebo supplementation. Results: No significant difference in FMD response and StO₂ parameters was observed after MC and placebo (p > 0.05). Conclusions: A single dose of MC did not change FMD and muscle StO₂ parameters after eccentric exercise in healthy individuals. Full article

Background: Perivascular adipose tissue (PVAT) attenuation has emerged as a novel biomarker for identifying high-risk arterial plaques due to its association with inflammation. Recognizing the systemic nature of atherosclerosis and its link with major cardiovascular events in coronary disease, this study evaluated PVAT attenuation in the peripheral arteries using CT imaging to expand the understanding of its diagnostic and prognostic potential. Methods: a retrospective analysis of 53 consecutive patients who underwent CT angiography, examining PVAT density across five primary peripheral arterial segments. A 5 mm region of interest adjacent to the vascular wall was analyzed by two blinded readers, with reproducibility coefficients calculated to determine the reliability of the measurements. For the statistical analyses, mean values were derived from these measurements. The patients were stratified into four groups based on the degree of arterial stenosis: <25%, 25–50%, 50–70%, and >70%. PVAT density comparisons between these groups were performed using the Kruskal–Wallis test and the pairwise Mann–Whitney U test with Holm–Bonferroni correction for multiple comparisons. Results: the Kruskal–Wallis test revealed statistically significant disparities in PVAT density across the categorically differentiated stenosis groups (p < 0.001), indicating an association between PVAT density and arterial stenosis severity. This association was especially pronounced in the external iliac, common femoral, superficial femoral, and popliteal arteries, where the p-values were consistently below 0.05. Subsequent pairwise analyses utilizing the Mann–Whitney U test with Holm–Bonferroni correction affirmed these findings, in particular for the external iliac, common femoral, superficial femoral and popliteal arteries (p < 0.05). Conclusions: our findings reinforce the correlation between increased PVAT density and the degree of arterial stenosis, supporting the clinical value of PVAT as a non-invasive biomarker for cardiovascular risk stratification and potentially guiding therapeutic interventions. Full article

This retrospective study examines 248 test bolus examinations preceding contrast-enhanced magnetic resonance angiography (CE-MRA) to extract clinically relevant data for critical limb ischemia (CLI) management. The method involved a retrospective review of test bolus exams, analysing 60 graphs for time to peak (TTP), full-width half-maximum (FWHM) time, and time to continual rise in signal intensity. These values were correlated with heart function parameters (ejection fraction, ASA classification, Lee index, and MET score). The results indicate a mean TTP of 31.2 ± 7.3 s, showing a correlation between the ejection fraction and ASA classification. Patients with atrial fibrillation exhibited prolonged TTP compared to those without. Despite population heterogeneity, these findings facilitate risk stratification for limb-saving interventions in CLI. TTP emerges as a potential clinical cardiovascular parameter and a risk factor for vascular interventions. Given the variation in injection protocols across centres, this study underscores the importance of precise bolus arrival time documentation for future multicentre studies. Full article

Glycine, a simple amino acid, is not only essential due to its potential insufficiency in vivo, but also has significant metabolic functions. It serves as a crucial building block for proteins. At the same time, as a bioactive molecule, it regulates gene expression for cytoprotection, protein configuration and activity, and other critical biological processes, including glutathione synthesis. The intriguing, beneficial effects of glycine in medical applications have piqued the research community’s interest in recent decades. This work delves into the compelling discoveries about the pivotal role of glycine in cardiovascular health and its intricate mechanisms of action for alleviating several medical conditions. Glycine’s broad spectrum of impact spans numerous diseases, encompassing not only acute myocardial infarction, aortic dissection, and cardiac hypertrophy, but also transplant rejections of aortic allografts, insulin resistance, and endothelial dysfunction, thereby providing a comprehensive understanding of its medical applications. Full article