Y Chromosome, Hypertension and Cardiovascular Disease: Is Inflammation the Answer?

Khan, Shanzana I.; Andrews, Karen L.; Jennings, Garry; Sampson, Amanda K.; Chin-Dusting, Jaye

doi:10.3390/ijms20122892

Cited by 26 publications

(20 citation statements)

References 79 publications

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“…A higher occurrence of cardiovascular diseases in males is also a well-known phenomenon. 42 Our cohort is characterized by a remarkable predominance of locally advanced tumors: pT3 carcinoma represented 49.6% [45.4-53.7] and pT4 35.6% [31.7-39.7], but pT2 only 11.9% [9.5-14.9] of all cases. In parallel with this, we observed a high rate of perineural and lymphatic invasion, in contrast to previous studies in other countries.…”

Section: Discussionmentioning

confidence: 89%

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Briede¹,

Štrumfa²,

Vanags³

et al. 2020

JIR

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Background: Inflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence. Purpose and methods: The aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC. Results: There were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn's like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007). Conclusion: High-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.

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Section: Discussionmentioning

confidence: 89%

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Briede¹,

Štrumfa²,

Vanags³

et al. 2020

JIR

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“…78 Although the biological basis for these sex-related differences in hypertension remain unclear, sex hormones, Y chromosome, Ang II, aldosterone, and sex hormoneerelated signalling play a critical role. [79][80][81] In addition, growing evidence suggests that oxidative stress may be important in the sexual dimorphism in hypertension. 82 Both clinical and preclinical studies have demonstrated that biomarkers of oxidative stress are higher in men than in women.…”

Section: Oxidative Stress Sex and Hypertensionmentioning

confidence: 99%

Oxidative Stress: A Unifying Paradigm in Hypertension

Touyz

Ríos

Alves-Lopes

et al. 2020

Canadian Journal of Cardiology

188

129

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The etiology of hypertension involves complex interactions among genetic, environmental, and pathophysiologic factors that influence many regulatory systems. Hypertension is characteristically associated with vascular dysfunction, cardiovascular remodelling, renal dysfunction, and stimulation of the sympathetic nervous system. Emerging evidence indicates that the immune system is also important and that activated immune cells migrate and accumulate in tissues promoting inflammation, fibrosis, and target-organ damage. Common to these processes is oxidative stress, defined as an imbalance between

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“…Although the mechanism by which the Y chromosome influences heterochromatin/ euchromatin content and thus the transcription of the other genes is largely unknown, one of the hypotheses postulates that the Y chromosome sequesters heterochromatinization factors and another that it affects the architecture of cell nucleus, which makes specific genes inaccessible to the transcription factors [19][20][21][22]. Phylogenetic studies showed that the males with the haplogroup I, which is one of the most popular European lineages of the Y chromosome, have upregulated inflammatory response, downregulated adaptive immunity, and a higher risk of coronary diseases [23][24][25]. In the murine models, Y chromosomes influence the number of natural killer T cells, the gene expression pattern in CD4 + T cells, the immune response of macrophages, and the mortality rate following the infection with coxsackievirus [26][27][28], which argues for the strong impact of the Y chromosome on a large variety of immune cells and immune processes.…”

Section: Y Chromosomementioning

confidence: 99%

The Role of Genetic Sex and Mitochondria in Response to COVID-19 Infection

Kloc

Ghobrial

Kubiak

2020

Int Arch Allergy Immunol

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The difference between the female and male immune response to COVID-19 infection, and infections in general, is multifactorial. The well-known determiners of the immune response, such as X and Y chromosomes, sex hormones, and microbiota, are functionally interconnected and influence each other in shaping the organism's immunity. We focus our commentary on the interplay between the genetic sex and mitochondria and how this may affect a sex-dependent immune response in COVID-19 infection. Realizing the existence of these interactions may help in designing novel methods or fine-tuning the existing and routine therapies to fight COVID-19 and other infections.

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Y Chromosome, Hypertension and Cardiovascular Disease: Is Inflammation the Answer?

Cited by 26 publications

References 79 publications

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Oxidative Stress: A Unifying Paradigm in Hypertension

The Role of Genetic Sex and Mitochondria in Response to COVID-19 Infection

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