Chronic venous insufficiency and varicose veins occur commonly in affluent countries and are a socioeconomic burden. However, there remains a relative lack of knowledge about venous pathophysiology. Various theories have been suggested, yet the molecular sequence of events is poorly understood. Transforming growth factor-beta one (TGF-β1) is a highly complex polypeptide with multifunctional properties that has an active role during embryonic development, in adult organ physiology and in the pathophysiology of major diseases, including cancer and various autoimmune, fibrotic and cardiovascular diseases. Therefore, an emphasis on understanding its signaling pathways (and possible disruptions) will be an essential requirement for a better comprehension and management of specific diseases. This review aims at shedding more light on venous pathophysiology by describing the TGF-β1 structure, function, activation and signaling, and providing an overview of how this growth factor and disturbances in its signaling pathway may contribute to specific pathological processes concerning the vessel wall which, in turn, may have a role in chronic venous insufficiency.

Chronic venous disease (CVeD) is a prevalent condition with a significant socioeconomic burden, yet the pathophysiology is only just beginning to be understood. Previous studies concerning the dysregulation of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) within the varicose vein wall are inconsistent and disregard clinical progression. Moreover, it is highly plausible that MMP and TIMP expression/activity is affected by transforming growth factor (TGF)-β1 and its signaling receptors (TGFβRs) expression/activity in the vein wall. A case–control study was undertaken to analyze genetic and immunohistochemical differences between healthy (n = 13) and CVeD (early stages: n = 19; advanced stages: n = 12) great saphenous vein samples. Samples were grouped based on anatomic harvest site and subjected to quantitative polymerase chain reaction for MMP1, MMP2, MMP8, MMP9, MMP12, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, TGFβR1, TGFβR2, and TGFβR3 gene expression analysis, and then to immunohistochemistry for immunolocalization of MMP2, TIMP2, and TGFβR2. Decreased gene expression of MMP12, TIMP2, TIMP3, TIMP4, and TGFβR2 was found in varicose veins when compared to controls. Regarding CVeD clinical progression, two facts arose: results across anatomical regions were uneven; decreased gene expression of MMP9 and TGFβR3 and increased gene expression of MMP2 and TIMP3 were found in advanced clinical stages. Most immunohistochemistry results for tunica intima were coherent with qPCR results. In conclusion, decreased expression of TGFβRs might suggest a reduction in TGF-β1 participation in the MMP/TIMP imbalance throughout CVeD progression. Further studies about molecular events in the varicose vein wall are required and should take into consideration the venous anatomical region and CVeD clinical progression.

Objectives: Transforming growth factor-beta1 (TGF-β1) may participate in local chronic inflammatory processes in varicose veins and in venous wall structure modifications through regulation of matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitor of metalloproteinase (TIMP)). The aim of this study was to analyze the effect of TGF-β1 in the vein wall, namely on the gene expression of selected MMP, TIMP and TGF-β1 receptors. Methods: Healthy vein samples were harvested from eight subjects who underwent coronary bypass graft surgery with great saphenous vein. Each vein sample was divided into two segments, which were cultivated separately in vitro (one of the segments had TGF-β1 added) and then submitted to gene expression analysis. Results: In the TGF-β1 supplemented group, there was a general increase in the mean gene expression. Specifically, expression of MMP9, MMP12, TIMP1 and TIMP2 were statistically significant. Conclusion: The results of this study demonstrate that the gene expression of MMP9, MMP12, TIMP1 and TIMP2 was influenced by the addition of TGF-β1. These results may be translated to chronic venous insufficiency framework and suggest involvement of TGF-β1 in the vein wall pathology.

MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression and have been implicated in various physiological and pathological processes, including cardiovascular diseases. The clinical presentation, diagnostic criteria, and proposed pathophysiological mechanisms of Takotsubo Syndrome (TTS) are discussed, with an emphasis on the emerging evidence implicating miRNAs in its etiology and progression. A systematic review following the PRISMA guidelines was performed on the evidence regarding the interplay between miRNAs and TTS. A search of the Pubmed, Web of Science, and Scopus databases was conducted and resulted in 584 articles. Of these, 14 full-text articles were eligible for inclusion in the qualitative analysis. The reviewed studies suggest that multiple miRNAs are involved in the processes associated with TTS pathophysiology, including acute and chronic myocardial inflammation, oxidative stress, apoptosis, microvascular dysfunction, hypertrophy, and, ultimately, maladaptive cardiac remodelling. This review provides an overview of the current understanding of miRNAs in cardiovascular pathophysiology, with a specific focus on their potential roles in TTS. To the best of our knowledge, this is the first systematic exploration of the miRNAs involved in TTS and its modulation as potential biomarkers or therapeutic targets.

A study of 701 primary adenocarcinomas of the lung was made at the Department of Pathology of the Hospital da Universidade de Coimbra for a period of fifteen years, between 1990 and 2004. In the same period 382 metastases were diagnosed, mainly from colon (119) and breast (66). The incidence of primary adenocarcinomas varied from 16 cases in 1990 to 49 cases in men and from 12 to 37 cases in women in that period. From 2001 onwards, the incidence was almost coincident in both genders. In the last four years, since 2001, patients were in the seventies at the time of diagnosis and a considerable number of cases were diagnosed after 80 years of age. The criteria defined by the WHO classification of Tumours of the Lung, Pleura, Thymus and Heart 2004 were applied to the primary adenocarcinomas of the lung and as was expected, bronchioloalveolar carcinomas had its incidence in women while acinar adenocarcinomas were diagnosed mainly in men. These conclusions were obtained via surgical specimens and when surgical biopsies were representative and those were mainly in stage IIB and IIIA. A number of 109 cases had the final diagnosis of adenocarcinoma of the lung based on morphology and immunohistochemistry criteria.