Multidisciplinary follow-up in a patient with Morgagni hernia leads to diagnosis of Marfan syndrome.

BACKGROUND: congenital diaphragmatic hernia (CDH) is a birth defect occurring in isolated or syndromic (chromosomal or monogenic) conditions. The diaphragmatic defect can be the most common one: left-sided posterolateral, named Bochdalek hernia; or it can be an anterior-retrosternal defect, named Morgagni hernia. Marfan syndrome (MFS) is a rare autosomal dominant inherited condition that affects connective tissue, caused by mutations in fibrillin-1 gene on chromosome 15. To date various types of diaphragmatic defects (about 30 types) have been reported in association with MFS, but they are heterogeneous, including CDH and paraesophageal hernia. CASE PRESENTATION: We describe the case of a child incidentally diagnosed with Morgagni hernia through a chest X-ray performed due to recurrent respiratory tract infections. Since the diagnosis of CDH, the patient underwent a clinical multidisciplinary follow-up leading to the diagnosis of MFS in accordance with revised Ghent Criteria: the child had typical clinical features and a novel heterozygous de novo single-base deletion in exon 26 of the FBN1 gene, identified by Whole-Exome Sequencing. MFS diagnosis permitted to look for cardiovascular complications and treat them, though asymptomatic, in order to prevent major cardiovascular life-threatening events. CONCLUSION: Our case shows the importance of a long-term and multidisciplinary follow-up in all children with diagnosis of CDH.

Antimicrobial Peptides towards Clinical Application-A Long History to Be Concluded.

Antimicrobial peptides (AMPs) are molecules with an amphipathic structure that enables them to interact with bacterial membranes. This interaction can lead to membrane crossing and disruption with pore formation, culminating in cell death. They are produced naturally in various organisms, including humans, animals, plants and microorganisms. In higher animals, they are part of the innate immune system, where they counteract infection by bacteria, fungi, viruses and parasites. AMPs can also be designed de novo by bioinformatic approaches or selected from combinatorial libraries, and then produced by chemical or recombinant procedures. Since their discovery, AMPs have aroused interest as potential antibiotics, although few have reached the market due to stability limits or toxicity. Here, we describe the development phase and a number of clinical trials of antimicrobial peptides. We also provide an update on AMPs in the pharmaceutical industry and an overall view of their therapeutic market. Modifications to peptide structures to improve stability in vivo and bioavailability are also described.

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression.

Despite the evident progress in neonatal medicine, retinopathy of prematurity (ROP) remains a serious threat to the vision of premature infants, due to a still partial understanding of the mechanisms underlying the development of this disease and the lack of drugs capable of arresting its progression. Although ROP is a multifactorial disease, retinal vascularization is strictly dependent on oxygen concentration. The exposition of the retina of a preterm newborn, still incompletely vascularized, to an atmosphere relatively hyperoxic, as the extrauterine environment, induces the downregulation of proangiogenic factors and therefore the interruption of vascularization (first ischemic phase of ROP). However, over the following weeks, the growing metabolic requirement of this ischemic retina produces a progressive hypoxia that specularly promotes the surge of proangiogenic factors, finally leading to proliferative retinopathy (second proliferative phase of ROP). The demonstration that the noradrenergic system is actively involved in the coupling between hypoxia and the induction of vasculogenesis paved the way for a pharmacologic intervention aimed at counteracting the interaction of noradrenaline with specific receptors and consequently the progression of ROP. A similar trend has been observed in infantile hemangiomas, the most common vascular lesion of childhood induced by pre-existing hypoxia, which shares similar characteristics with ROP. The fact that propranolol, an unselective antagonist of ß1/2 adrenoceptors, counteracts the growth of infantile hemangiomas, suggested the idea of testing the efficacy of propranolol in infants with ROP. From preclinical studies, ongoing clinical trials demonstrated that topical administration of propranolol likely represents the optimal approach to reconcile its efficacy and maximum safety. Given the strict relationship between vessels and neurons, recovering retinal vascularization with propranolol may add further efficacy to prevent retinal dysfunction. In conclusion, the strategy of contrasting precociously the progression of the disease appears to be more advantageous than the current wait-and-see therapeutic approach, which instead is mainly focused on avoiding retinal detachment.

ß3 Adrenoceptor Agonism Prevents Hyperoxia-Induced Colonic Alterations.

Oxygen level is a key regulator of organogenesis and its modification in postnatal life alters the maturation process of organs, including the intestine, which do not completely develop in utero. The ß3-adrenoreceptor (ß3-AR) is expressed in the colon and has an oxygen-dependent regulatory mechanism. This study shows the effects of the ß3-AR agonist BRL37344 in a neonatal model of hyperoxia-driven colonic injury. For the first 14 days after birth, Sprague-Dawley rat pups were exposed to ambient oxygen levels (21%) or hyperoxia (85%) and treated daily with BRL37344 at 1, 3, 6 mg/kg or untreated. At the end of day 14, proximal colon samples were collected for analysis. Hyperoxia deeply influences the proximal colon development by reducing ß3-AR-expressing cells (27%), colonic length (26%) and mucin production (47%), and altering the neuronal chemical coding in the myenteric plexus without changes in the neuron number. The administration of BRL37344 at 3 mg/kg, but not at 1 mg/kg, significantly prevented these alterations. Conversely, it was ineffective in preventing hyperoxia-induced body weight loss. BRL37344 at 6 mg/kg was toxic. These findings pave the way for ß3-AR pharmacological targeting as a therapeutic option for diseases caused by hyperoxia-impaired development, typical prematurity disorders.

Fetal Oxygenation from the 23rd to the 36th Week of Gestation Evaluated through the Umbilical Cord Blood Gas Analysis.

The embryo and fetus grow in a hypoxic environment. Intrauterine oxygen levels fluctuate throughout the pregnancy, allowing the oxygen to modulate apparently contradictory functions, such as the expansion of stemness but also differentiation. We have recently demonstrated that in the last weeks of pregnancy, oxygenation progressively increases, but the trend of oxygen levels during the previous weeks remains to be clarified. In the present retrospective study, umbilical venous and arterial oxygen levels, fetal oxygen extraction, oxygen content, CO2, and lactate were evaluated in a cohort of healthy newborns with gestational age < 37 weeks. A progressive decrease in pO2 levels associated with a concomitant increase in pCO2 and reduction in pH has been observed starting from the 23rd week until approximately the 33-34th week of gestation. Over this period, despite the increased hypoxemia, oxygen content remains stable thanks to increasing hemoglobin concentration, which allows the fetus to become more hypoxemic but not more hypoxic. Starting from the 33-34th week, fetal oxygenation increases and ideally continues following the trend recently described in term fetuses. The present study confirms that oxygenation during intrauterine life continues to vary even after placenta development, showing a clear biphasic trend. Fetuses, in fact, from mid-gestation to near-term, become progressively more hypoxemic. However, starting from the 33-34th week, oxygenation progressively increases until birth. In this regard, our data suggest that the placenta is the hub that ensures this variable oxygen availability to the fetus, and we speculate that this biphasic trend is functional for the promotion, in specific tissues and at specific times, of stemness and intrauterine differentiation.

Case report: Complex arterial findings in vascular ehlers-danlos syndrome with a novel COL3A1 variant and death at young age.

Vascular Ehlers-Danlos syndrome (vEDS) is a genetic disease caused by a pathogenic mutation in the COL3A1 gene. Despite its severe course, the rarity and extreme clinical variability of the disease can pose significant obstacles to a timely diagnosis. Early and accurate diagnosis may lead to improved patient outcomes by providing access to targeted pharmacological treatments like celiprolol and enhancing the management of vEDS-related complications. Herein, we report a patient harboring a novel de novo COL3A1 missense variant, in which the diagnosis was only possible belatedly due to delayed referral for genetic evaluation. The patient developed pulmonary complications, aneurysms, and vascular malformations, and died at the age of 26 years due to massive pulmonary bleeding.

Marfan Syndrome: Enhanced Diagnostic Tools and Follow-up Management Strategies.

Marfan syndrome (MFS) is a rare inherited autosomic disorder, which encompasses a variety of systemic manifestations caused by mutations in the Fibrillin-1 encoding gene (FBN1). Cardinal clinical phenotypes of MFS are highly variable in terms of severity, and commonly involve cardiovascular, ocular, and musculoskeletal systems with a wide range of manifestations, such as ascending aorta aneurysms and dissection, mitral valve prolapse, ectopia lentis and long bone overgrowth, respectively. Of note, an accurate and prompt diagnosis is pivotal in order to provide the best treatment to the patients as early as possible. To date, the diagnosis of the syndrome has relied upon a systemic score calculation as well as DNA mutation identification. The aim of this review is to summarize the latest MFS evidence regarding the definition, differences and similarities with other connective tissue pathologies with severe systemic phenotypes (e.g., Autosomal dominant Weill-Marchesani syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome) and clinical assessment. In this regard, the management of MFS requires a multidisciplinary team in order to accurately control the evolution of the most severe and potentially life-threatening complications. Based on recent findings in the literature and our clinical experience, we propose a multidisciplinary approach involving specialists in different clinical fields (i.e., cardiologists, surgeons, ophthalmologists, orthopedics, pneumologists, neurologists, endocrinologists, geneticists, and psychologists) to comprehensively characterize, treat, and manage MFS patients with a personalized medicine approach.

Seroprevalence of SARS-CoV-2 antibodies and retrospective mortality in two African settings: Lubumbashi, Democratic Republic of the Congo and Abidjan, Côte d'Ivoire.

Although seroprevalence studies have demonstrated the wide circulation of SARS-COV-2 in African countries, the impact on population health in these settings is still poorly understood. Using representative samples of the general population, we evaluated retrospective mortality and seroprevalence of anti-SARS-CoV-2 antibodies in Lubumbashi and Abidjan. The studies included retrospective mortality surveys and nested anti-SARS-CoV-2 antibody prevalence surveys. In Lubumbashi the study took place during April-May 2021 and in Abidjan the survey was implemented in two phases: July-August 2021 and October-November 2021. Crude mortality rates were stratified between pre-pandemic and pandemic periods and further investigated by age group and COVID waves. Anti-SARS-CoV-2 seroprevalence was quantified by rapid diagnostic testing (RDT) and laboratory-based testing (ELISA in Lubumbashi and ECLIA in Abidjan). In Lubumbashi, the crude mortality rate (CMR) increased from 0.08 deaths per 10 000 persons per day (pre-pandemic) to 0.20 deaths per 10 000 persons per day (pandemic period). Increases were particularly pronounced among <5 years old. In Abidjan, no overall increase was observed during the pandemic period (pre-pandemic: 0.05 deaths per 10 000 persons per day; pandemic: 0.07 deaths per 10 000 persons per day). However, an increase was observed during the third wave (0.11 deaths per 10 000 persons per day). The estimated seroprevalence in Lubumbashi was 15.7% (RDT) and 43.2% (laboratory-based). In Abidjan, the estimated seroprevalence was 17.4% (RDT) and 72.9% (laboratory-based) during the first phase of the survey and 38.8% (RDT) and 82.2% (laboratory-based) during the second phase of the survey. Although circulation of SARS-CoV-2 seems to have been extensive in both settings, the public health impact varied. The increases, particularly among the youngest age group, suggest indirect impacts of COVID and the pandemic on population health. The seroprevalence results confirmed substantial underdetection of cases through the national surveillance systems.

Fetal oxygenation in the last weeks of pregnancy evaluated through the umbilical cord blood gas analysis.

Introduction: Embryo and fetus grow and mature over the first trimester of pregnancy in a dynamic hypoxic environment, where placenta development assures an increased oxygen availability. However, it is unclear whether and how oxygenation changes in the later trimesters and, more specifically, in the last weeks of pregnancy. Methods: Observational study that evaluated the gas analysis of the umbilical cord blood collected from a cohort of healthy newborns with gestational age ≥37 weeks. Umbilical venous and arterial oxygen levels as well as fetal oxygen extraction were calculated to establish whether oxygenation level changes over the last weeks of pregnancy. In addition, fetal lactate, and carbon dioxide production were analyzed to establish whether oxygen oscillations may induce metabolic effects in utero. Results: This study demonstrates a progressive increase in fetal oxygenation levels from the 37th to the 41st weeks of gestation (mean venous PaO2 approximately from 20 to 25 mmHg; p < 0.001). This increase is largely attributable to growing umbilical venous PaO2, regardless of delivery modalities. In neonates born by vaginal delivery, the increased oxygen availability is associated with a modest increase in oxygen extraction, while in neonates born by cesarean section, it is associated with reduced lactate production. Independently from the type of delivery, carbon dioxide production moderately increased. These findings suggest a progressive shift from a prevalent anaerobic metabolism (Warburg effect) towards a growing aerobic metabolism. Conclusion: This study confirms that fetuses grow in a hypoxic environment that becomes progressively less hypoxic in the last weeks of gestation. The increased oxygen availability seems to favor aerobic metabolic shift during the last weeks of intrauterine life; we hypothesize that this environmental change may have implications for fetal maturation during intrauterine life.

In Vivo Efficacy and Toxicity of an Antimicrobial Peptide in a Model of Endotoxin-Induced Pulmonary Inflammation.

SET-M33 is a synthetic peptide that is being developed as a new antibiotic against major Gram-negative bacteria. Here we report two in vivo studies to assess the toxicity and efficacy of the peptide in a murine model of pulmonary inflammation. First, we present the toxicity study in which SET-M33 was administered to CD-1 mice by snout inhalation exposure for 1 h/day for 7 days at doses of 5 and 20 mg/kg/day. The results showed adverse clinical signs and effects on body weight at the higher dose, as well as some treatment-related histopathology findings (lungs and bronchi, nose/turbinates, larynx and tracheal bifurcation). On this basis, the no observable adverse effect level (NOAEL) was considered to be 5 mg/kg/day. We then report an efficacy study of the peptide in an endotoxin (LPS)-induced pulmonary inflammation model. Intratracheal administration of SET-M33 at 0.5, 2 and 5 mg/kg significantly inhibited BAL neutrophil cell counts after an LPS challenge. A significant reduction in pro-inflammatory cytokines, KC, MIP-1α, IP-10, MCP-1 and TNF-α was also recorded after SET-M33 administration.

COVID-19 Vaccine Hesitancy in Italian Adults with Marfan Syndrome: Insights from a Secondary Analysis of a Cross-Sectional Study.

Although vaccine hesitancy has been reported in many patient groups and countries, there is a lack of data on vaccine hesitancy in patients with Marfan syndrome (MFS). MFS is a rare genetic disorder that can lead to cardiovascular, ocular, and musculoskeletal issues. Because MFS patients may face an increased risk of COVID-19 complications, vaccination is crucial for this population. This brief report aims to describe vaccine hesitancy rates in MFS patients and compare the characteristics of patients who are hesitant and those who are not to gain a better understanding of this specific population. This study analyzes previously published cross-sectional data that examined mental health, sociodemographic, and clinical factors associated with PTSD, depression, anxiety, and insomnia in MFS patients during the third wave of the COVID-19 pandemic in Lombardy, Italy. Of the 112 MFS patients who participated, 26 (23.9%) reported vaccine hesitancy. Vaccine hesitancy may be associated mainly with younger age and not be related to other patient characteristics. Therefore, this report found no differences in individual-level variables, such as sex, education, comorbidities, and mental health symptoms, between those who were hesitant and those who were not. The study findings are insightful and suggest that interventions to address vaccine hesitancy in this population may need to focus on attitudes and beliefs related to vaccination rather than targeting specific sociodemographic or clinical factors.

ß3-adrenergic receptor on tumor-infiltrating lymphocytes sustains IFN-γ-dependent PD-L1 expression and impairs anti-tumor immunity in neuroblastoma.

Neuroblastoma (NB) is a heterogeneous extracranial tumor occurring in childhood. A distinctive feature of NB tumors is their neuroendocrine ability to secrete catecholamines, which in turn, via ß-adrenergic receptors ligation, may affect different signaling pathways in tumor microenvironment (TME). It was previously demonstrated that specific antagonism of ß3-adrenergic receptor (ß3-AR) on NB tumor cells affected tumor growth and progression. Here, in a murine syngeneic model of NB, we aimed to investigate whether the ß3-AR modulation influenced the host immune system response against tumor. Results demonstrated that ß3-AR antagonism lead to an immune response reactivation, partially dependent on the PD-1/PD-L1 signaling axis involvement. Indeed, ß3-AR blockade on tumor-infiltrating lymphocytes (TILs) dampened their ability to secrete IFN-γ, which in turn reduced the PD-L1 expression, caused by TILs infiltration, on NB tumor cells. Further investigations, through a genomic analysis on NB patients, showed that high ADRB3 gene expression correlates with worse clinical outcome compared to the low expression group, and that ADRB3 gene expression affects different immune-related pathways. Overall, results indicate that ß3-AR in NB TME is able to modulate the interaction between tumor and host immune system, and that its antagonism hits multiple pro-tumoral signaling pathways.

Describing post-traumatic stress disorder and its associations with depression, anxiety and insomnia: a descriptive study in Italian adults with Marfan syndrome during the COVID-19 third wave.

OBJECTIVE: The evaluation of post-traumatic stress disorder (PTSD), depression, anxiety and insomnia in patients with Marfan syndrome (MFS) during the third wave of the COVID-19 pandemic in a region of northern Italy (Lombardy) and the investigation of which mental health, sociodemographic and clinical factors were associated with PTSD. DESIGN: Descriptive observational design with cross-sectional data collection procedure. SETTING: A single Italian MFS-specific specialised and reference centre in Lombardy (Italy) between February and April 2021. PARTICIPANTS: 112 adults with MFS. The majority of participants were female (n=64; 57.1%), with a high school diploma (n=52; 46.4%) and active workers (n=66; 58.9%). The mean age was 41.89 years (SD=14.00), and the mean time from diagnosis was 15.18 years (SD=11.91). PRIMARY AND SECONDARY OUTCOMES: Descriptive statistics described PTSD, which was the primary outcome, as well as depression, anxiety and insomnia, which were the secondary outcomes. Four linear regression models described the predictors of PTSD total score and its three domains: avoidance, intrusion and hyperarousal. RESULTS: One out of 10 patients with MFS had mild psychological symptoms regarding depression, anxiety and insomnia, and scores of PTSD that indicated clinical worries about the mental health status. The presence of PTSD was mainly predicted by anxiety (ß=0.647; p<0.001), being older, taking psychoactive medication and being unemployed. CONCLUSION: Depression, anxiety and insomnia should be monitored in patients with MFS in order to minimise PTSD insurgence. Specific psychosocial interventions should be developed and tested for this population and adopted in clinical practice, given the relevance of mental health outcomes during the pandemic.

Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases.

In recent years, we have discovered Esc(1-21) and its diastereomer (Esc peptides) as valuable candidates for the treatment of Pseudomonas lung infection, especially in patients with cystic fibrosis (CF). Furthermore, engineered poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were revealed to be a promising pulmonary delivery system of antimicrobial peptides. However, the "ad hoc" development of novel therapeutics requires consideration of their stability, tolerability, and safety. Hence, by means of electrophysiology experiments and preclinical studies on healthy mice, we demonstrated that neither Esc peptides or Esc-peptide-loaded PLGA NPs significantly affect the integrity of the lung epithelium, nor change the global gene expression profile of lungs of treated animals compared to those of vehicle-treated animals. Noteworthy, the Esc diastereomer endowed with the highest antimicrobial activity did not provoke any pulmonary pro-inflammatory response, even at a concentration 15-fold higher than the efficacy dosage 24 h after administration in the free or encapsulated form. The therapeutic index was ≥70, and the peptide was found to remain available in the bronchoalveolar lavage of mice, after two days of incubation. Overall, these studies should open an avenue for a new up-and-coming pharmacological approach, likely based on inhalable peptide-loaded NPs, to address CF lung disease.

Adenosine A3 Receptor (A3AR) Agonist for the Treatment of Bleomycin-Induced Lung Fibrosis in Mice.

Adenosine receptors (ARs) are involved in the suppression and development of inflammatory and fibrotic conditions. Specifically, AR activation promotes differentiation of lung fibroblasts into myofibroblasts, typical of a fibrotic event. Pulmonary fibrosis is a severe disease characterized by inflammation and fibrosis of unknown etiology and lacking an effective treatment. The present investigation explored the action of MRS5980, a new, highly potent and selective A3AR agonist, in an established murine model of lung fibrosis. The effects of either vehicle or MRS5980 were studied in mice following intratracheal bleomycin administration. We evaluated the role of the A3AR agonist on lung stiffness, studying the airway resistance to inflation, oxidative stress (8-OHdG and MDA), inflammation, pro- and anti-inflammatory marker levels (IL-1ß, IL-6, TNF-α, IL-10 and IL-17A) and fibrosis establishment, evaluating transforming growth factor (TGF)-ß expression and α-smooth muscle actin (α-SMA) deposition in lungs. Bleomycin administration increased lung stiffness, TGF-ß levels, α-SMA deposition, and inflammatory and oxidative stress markers. The treatment with MRS5980 attenuated all the analyzed functional, biochemical and histopathological markers in a dose-dependent manner. Our findings support the therapeutic potential of A3AR agonists in lung fibrosis by demonstrating reduced disease progression, as indicated by decreased inflammation, TGF-ß expression and fibrotic remodeling.

Safety evaluations of a synthetic antimicrobial peptide administered intravenously in rats and dogs.

The antimicrobial peptide SET-M33 is under study for the development of a new antibiotic against major Gram-negative pathogens. Here we report the toxicological evaluation of SET-M33 administered intravenously to rats and dogs. Dose range finding experiments determined the doses to use in toxicokinetic evaluation, clinical biochemistry analysis, necroscopy and in neurological and respiratory measurements. Clinical laboratory investigations in dogs and rats showed a dose-related increase in creatinine and urea levels, indicating that the kidneys are the target organ. This was also confirmed by necroscopy studies of animal tissues, where signs of degeneration and regeneration were found in kidney when SET-M33 was administered at the highest doses in the two animal species. Neurological toxicity measurements by the Irwin method and respiratory function evaluation in rats did not reveal any toxic effect even at the highest dose. Finally, repeated administration of SET-M33 by short infusion in dogs revealed a no-observed-adverse-effect-level of 0.5 mg/kg/day.

Antimicrobial Peptides Active in In Vitro Models of Endodontic Bacterial Infections Modulate Inflammation in Human Cardiac Fibroblasts.

Endodontic and periodontal disease are conditions of infectious origin that can lead to tooth loss or develop into systemic hyperinflammation, which may be associated with a wide variety of diseases, including cardiovascular. Endodontic and periodontal treatment often relies on antibiotics. Since new antimicrobial resistances are a major threat, the use of standard antibiotics is not recommended when the infection is only local. Antimicrobial peptides were recently demonstrated to be valid alternatives for dental treatments. The antimicrobial peptide M33D is a tetrabranched peptide active against Gram-negative and Gram-positive bacteria. It has a long life, unusual for peptides, because its branched form provides resistance to proteases. Here the efficacy of M33D and of its analog M33i/l as antibiotics for local use in dentistry was evaluated. M33D and M33i/l were active against reference strains and multidrug-resistant clinical isolates of Gram-negative and Gram-positive species. Their minimum inhibitory concentration against different strains of dental interest was between 0.4 and 6.0 µM. Both peptides acted rapidly on bacteria, impairing membrane function. They also disrupted biofilm effectively. Disinfection of the root canal is crucial for endodontic treatments. M33D and M33i/l reduced E. faecalis colonies to one-twentieth in a dentin slices model reproducing root canal irrigation. They both captured and neutralized lipopolysaccharide (LPS), a bacterial toxin responsible for inflammation. The release of IL-1ß and TNFα by LPS-stimulated murine macrophages was reduced by both peptides. Human cardiac fibroblasts respond to different insults with the release of proinflammatory cytokines, and consequently, they are considered directly involved in atherogenic cardiovascular processes, including those triggered by infections. The presence of M33D and M33i/l at MIC concentration reduced IL6 release from LPS- stimulated human cardiac fibroblasts, hence proving to be promising in preventing bacteria-induced atherogenesis. The two peptides showed low toxicity to mammalian cells, with an EC50 one order of magnitude higher than the average MIC and low hemolytic activity. The development of antimicrobial peptides for dental irrigations and medication is a very promising new field of research that will provide tools to fight dental infections and their severe consequences, while at the same time protecting standard antibiotics from new outbreaks of antimicrobial resistance.

Alpha1-antitrypsin deficiency and cardiovascular disease: questions and issues of a debated relation.

Alpha1-antitrypsin (AAT) is one of the major inhibitors involved in protease/antiprotease homeostasis, and it is mainly produced by hepatocytes and pulmonary epithelial cells. Its deficiency, called alpha1-antitrypsin deficit (AATD), leads to severe hepatic and respiratory issues. Also, AAT is released into the bloodstream providing systemic anti-inflammatory effects. Apart from acting as an acute-phase anti-inflammatory protein, it can be a biomarker for monitoring disease evolution. A reduced or defective production leads to a loss of anti-inflammatory function, protease-antiprotease imbalance and cellular engorgement due to polymers deposition, with system-wide repercussions. This review aims to evaluate AATD condition in the major vessels of the head and neck, thoracic and abdominal districts. Also, a dedicated focus on autoimmune vascular diseases will be provided. A critical revision of the main literature findings starting from the 1980s until now has been performed. Studies conducted over the years have provided several contradictory pieces of evidence. Most authors acknowledge the protective and anti-inflammatory AAT role on the vascular endothelium. However, correlations between AATD and major arteries, cerebral and cardiovascular conditions, and autoimmune diseases remain unclear. Most studies recognize the role of AATD in vascular diseases but only as a cofactor inducing cellular and tissue structure impairments. However, this condition alone is not enough to determine new disease onset. Due to the opposing results reported over the years, there is still a considerable lack of knowledge on the role covered by AATD in vascular diseases. A renewed interest in this research field should be encouraged to grant new solid evidence and validate the putative role of AATD screening and replacement therapy as useful diagnostic and treatment tools.