Summary

Hypertension is a major public health concern worldwide because of its rising prevalence and concomitant risks of cardiovascular diseases. Coping strategies may encompass a full spectrum of clinical, epidemiological, experimental, and technological factors to inspire front-line practices and shape critical thinking. This entry collection aims to assemble entries of wealthy topics related to clinical, therapeutic, and population sciences of hypertension and cardiovascular diseases that could inform research scientists and healthcare professionals.

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Topic Review
Wnt Signaling to Vascular Complications in T2DM
Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents “mandatory damage” in the development of microvascular complications and only “introductory damage” in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. 
  • 1
  • 01 Jul 2022
Topic Review
Epigenetics and Congenital Heart Diseases
Congenital heart disease (CHD) is a frequent occurrence, with a prevalence rate of almost 1% in the general population. However, the pathophysiology of the anomalous heart development is still unclear in most patients screened. A definitive genetic origin, be it single-point mutation or larger chromosomal disruptions, only explains about 35% of identified cases. The precisely choreographed embryology of the heart relies on timed activation of developmental molecular cascades, spatially and temporally regulated through epigenetic regulation: chromatin conformation, DNA priming through methylation patterns, and spatial accessibility to transcription factors. This multi-level regulatory network is eminently susceptible to outside disruption, resulting in faulty cardiac development. Similarly, the heart is unique in its dynamic development: growth is intrinsically related to mechanical stimulation, and disruption of the intrauterine environment will have a direct impact on fetal embryology. These two converging axes offer new areas of research to characterize the cardiac epigenetic regulation and identify points of fragility in order to counteract its teratogenic consequences.
  • 19
  • 28 Jun 2022
Topic Review
Obstructive Sleep Apnea and Cardiovascular Disease
Among the mechanisms which explain the association between obstructive sleep apnea and myocardial infarction (MI), common risk factors include male sex, age, hypertension, obesity, and smoking. However, other direct effects of obstructive sleep apnea merit consideration. The combination of repetitive apnea–hypopnea, hypoxia, and arousal from sleep increases sympathetic activity, which is maintained during wakefulness, thus increasing myocardial oxygen demand. The mechanistic understanding which connects obstructive sleep apnea and cardiovascular disease is poorly understood due to the diverse and complicated elements of obstructive sleep apnea and the multiple other comorbid conditions (especially obesity) impacting cardiovascular health. When obstructive apnea or hypopnea occurs, the upper airway collapses throughout sleep, affecting a complete or partial interruption of airflow even with sustained respiratory struggle. The sympathetic tone is stimulated, and respiratory work increases as opposed to the closed upper airway, increasing negative intrathoracic pressure. Stimulation of the sympathetic tone across the parasympathetic system affects heart rate and blood pressure. Awakening from sleep terminates the asphyxia event, with re-establishing airflow and re-oxygenation but further increased sympathetic tone. Obstructive sleep apnea seems to be correlated with increased levels of inflammatory cytokines. Furthermore, metabolic dysregulation is observed in obstructive sleep apnea patients (with abnormalities in both fat and glucose metabolism. 
  • 21
  • 27 Jun 2022
Topic Review
Extracellular Vesicles in Atherothrombosis
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. The following content focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection.
  • 19
  • 24 Jun 2022
Topic Review
Rieske Iron-Sulfur Protein in COPD and Pulmonary Hypertension
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide. The development of pulmonary hypertension (PH) accounts for the high mortality rate in COPD patients. Recent studies from our laboratory and others have highlighted the important role of reactive oxygen species (ROS) signaling in the development of COPD and associated PH. ROS are primarily generated in mitochondrial complex III in pulmonary artery smooth muscle cells (PASMCs). Rieske iron-sulfur protein (RISP), a catalytic subunit of mitochondrial complex III, is the major player in the generation of ROS. RISP plays a critical role in pulmonary vasoconstriction, remodeling and hypertension. Here, the recent important findings involving the functional roles of RISP in COPD and associated PH and meticulously discuss its potential therapeutic target in these devastating lung diseases were summarized.
  • 24
  • 27 Jun 2022
Topic Review
Lp(a) Paradox in Diabetes Mellitus
Lipoprotein(a) (Lp(a)) is one of the strongest causal risk factors of atherosclerotic disease. It is rich in cholesteryl ester and composed of apolipoprotein B and apo(a). Plasma Lp(a) levels are determined by apo(a) transcriptional activity driven by a direct repeat (DR) response element in the apo(a) promoter under the control of (HNF)4α Farnesoid-X receptor (FXR) ligands play a key role in the downregulation of APOA expression. In vitro studies on the catabolism of Lp(a) have revealed that Lp(a) binds to several specific lipoprotein receptors; however, their in vivo role remains elusive. In patients suffering from Type-I diabetes mellitus (T1DM), provided they are metabolically well-controlled, Lp(a) plasma concentrations are directly comparable to healthy individuals. In contrast, there exists a paradox in T2DM patients, as many of these patients have reduced Lp(a) levels; however, they are still at an increased cardiovascular risk. The Lp(a) lowering mechanism observed in T2DM patients is most probably caused by mutations in the mature-onset diabetes of the young (MODY) gene and possibly other polymorphisms in key transcription factors of the apolipoprotein (a) gene (APOA).
  • 32
  • 19 Jun 2022
Topic Review
Antithrombotic Therapy Following Transcatheter Aortic Valve Replacement
Transcatheter aortic valve replacement (TAVR) is expanding towards a low-risk patient category as a result of technical advances and operators’ improved skills. However, the post-TAVR antithrombotic regimen remains challenging. Single antiplatelet therapy appears to be the best compromise when there is no compelling indication for chronic oral anticoagulation. Whether it should be aspirin or clopidogrel is not established. There is no supportive evidence to use oral anticoagulation when there is no established indication for oral anticoagulation other than the TAVR procedure. The gap in evidence as to whether DOACs should be preferred over VKA remains when there is an indication for oral anticoagulation (OAC) use. It seems that DOACs are not the same and randomized trials are awaited. Likewise, whether oral anticoagulant therapy should be continued or interrupted during the procedure remains unclear.
  • 26
  • 17 Jun 2022
Topic Review
Human Paraoxonase-2 (PON2)
PON1, PON2, and PON3 belong to a family of lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) involved in bacterial quorum-sensing signaling. Accordingly, defense against pathogens, such as Brevundimonas aeruginosa (B. aeruginosa), was postulated to be the principal function of PON2. Moreover, findings have highlighted the importance of PON2 in oxidative stress control, inhibition of apoptosis, and the progression of various types of malignancies.
  • 41
  • 17 Jun 2022
Topic Review
Red Wine Consumption and Cardiovascular Health
Wine is a popular alcoholic beverage that has been consumed for hundreds of years. Benefits from moderate alcohol consumption have been widely supported by the scientific literature and, in this line, red wine intake has been related to a lesser risk for coronary heart disease (CHD). Experimental studies and meta-analyses have mainly attributed this outcome to the presence in red wine of a great variety of polyphenolic compounds such as resveratrol, catechin, epicatechin, quercetin, and anthocyanin. Resveratrol is considered the most effective wine compound with respect to the prevention of CHD because of its antioxidant properties. The mechanisms responsible for its putative cardioprotective effects would include changes in lipid profiles, reduction of insulin resistance, and decrease in oxidative stress of low-density lipoprotein cholesterol (LDL-C). 
  • 47
  • 17 Jun 2022
Topic Review
Outlook on Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is characterized as a disorder of the heart muscle. It is distinguished by the widening/dilation of the left ventricle of the heart with left ventricular or biventricular systolic dysfunction. Contractile functioning of the left ventricle is highly compromised due to dilation. However, in some cases of DCM, the right ventricle is also dilated. Dilated cardiomyopathy (DCM) remains an enigmatic cardiovascular disease (CVD) condition characterized by contractile dysfunction of the myocardium due to dilation of the ventricles. DCM is one of the major forms of CVD contributing to heart failure. Dilation of the left or both ventricles with systolic dysfunction, not explained by known causes, is a hallmark of DCM. Progression of DCM leads to heart failure. Genetic and various other factors greatly contribute to the development of DCM, but the etiology has still remained elusive in a large number of cases. 
  • 22
  • 15 Jun 2022
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