Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.
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http://dx.doi.org/10.1097/HJH.0000000000003503 | DOI Listing |
Sci Rep
January 2025
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
Brain microvascular endothelial cells are connected by tight junction (TJ) proteins and interacted by adhesion molecules, which participate in the selective permeability of the blood-brain barrier (BBB). The disruption of BBB is associated with the progression of cerebral diseases. Pterostilbene is a natural compound found in blueberries and grapes with a wide range of biological activities, including anti-inflammatory, antioxidant, and anti-diabetic effects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
cheonan chungmu hospital, cheonan si, Korea, Republic of (South)
Background: Vascular contributions to dementia & Alzheimer’s disease are increasing recognized. Recent studies have suggested that blood‐brain barrier breakdown is an early biomarker of human cognitive dysfunction, including the early clinical stages of AD. Apolipoprotein E4(APOE4), the major AD susceptibility gene, leads to accelerated blood‐brain barrier breakdown & degeneration of brain capillary pericyte that maintain blood‐brain barrier integrity.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Longeveron Inc., Miami, FL, USA
Background: Alzheimer’s disease (AD) is characterized by progressive atrophy of the cerebral cortex and hippocampus, with concomitant increase in ventricular volume. Lomecel‐B is a novel cell‐based therapeutic approach to AD that targets neuroinflammation, microvascular dysfunction, and has the potential to stimulate endogenous tissue regeneration. We conducted MRI analysis of brain morphology in the CLEAR‐MIND study, a 49‐patient proof‐of‐concept study that tested 3 different dosing regimens of Lomecel‐B vs placebo in patients with mild AD dementia.
View Article and Find Full Text PDFCardiovasc Res
January 2025
State Key Laboratory of Cardiovascular Disease, Clinical Pharmacology Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
Aims: The therapeutic efficacy of coronary revascularization is compromised by myocardial ischemia-reperfusion (MI/R) injury. Higher levels of circulating arachidonic acid (AA) are reportedly associated with lower risk of cardiovascular disease. The cyclooxygenase (COX) pathway metabolizes AA into prostaglandins (PGs) and the platelet-activating thromboxane A2 (TXA2), which is inhibited by aspirin.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
January 2025
Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Lung infection is one of the leading causes of morbidity and mortality worldwide. Even with appropriate antibiotic and antiviral treatment, mortality in hospitalized patients often exceeds 10%, highlighting the need for the development of new therapeutic strategies. Of late, cystic fibrosis transmembrane conductance regulator (CFTR) is - in addition to its well-established roles in the lung airway and extrapulmonary organs - increasingly recognized as a key regulator of alveolar homeostasis and defense.
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