Abstract
According to the latest clinical data, cardiovascular diseases have ranked first in prone diseases, causing 40% of the premature deaths of China's population. This study aimed to investigate the influence of Toll-like receptor 2- (TLR2-) mediated inflammation on the occurrence and development of familial hypertension combined with hyperlipemia and its related mechanism. Blood specimens from 66 patients undergoing coronary atherosclerosis were collected and grouped, including 22 patients into the control group, 25 into the familial hypertension group, and 19 into familial hypertension combined with hyperlipemia group. In this study, ELISA was conducted for determining the levels of four inflammatory factors of TLR2 and IL-1β, IL-6, TNF-ɑ, and CCL2 in serum and the levels of relevant indicators in mice. C57Bl/6j and genetically engineered C.129(B6)-Tlr2tm1Kir/J mice were given subcutaneous injection of normal saline (wild-saline group), 8-week 40% high-fat diet (wild-high-fat group), and subcutaneous Alzet-implanted angiotensin II micropump supplemented with the research diet (wild-high fat-Ang II group, Tlr2-/--high fat-Ang II group). Blood pressure in mice was recorded consecutively with a noninvasive hemopiezometer for eight weeks. TLR2 and IL-1β, IL-6, TNF-ɑ, and CCL2 in serum of patients with familial hypertension combined with hyperlipemia and the hypertension combined with hyperlipemia mouse model were higher than those in the normal group. Under combined intervention of Ang II and the research diet, mRNA expression related to blood pressure, blood lipid, and fat metabolism in Tlr2-/- genetically engineering mice was significantly lower than that in the wild-high fat-Ang II group. The phosphorylation levels of AKT, IKK, and p65 in mice with hypertension combined with hyperlipidemia were significantly higher than those in normal group. The levels of blood pressure and blood lipid in mice after blocking the AKT or NF-κB pathway were significantly downregulated compared with those in the wild-high fat-Ang II group, with statistically significant differences (both P < 0.05). In conclusion, TLR2 regulates inflammation through Akt-NF-κB pathway, thus inducing the occurrence and development of familial hypertension combined with hyperlipemia.
Highlights
According to the latest clinical data, cardiovascular diseases have ranked first in prone diseases, causing 40% of the premature deaths of China’s population [1,2,3]
Except for related indicators of hypertension, hyperlipemia and medication, there were no statistical differences in age, gender distribution, smoking, previous history, and medication in the subjects of control, familial hypertension, and familial hypertension combined with hyperlipidemia groups
According to the results of ELISA for relevant indicators of blood specimen in serums, the levels of TLR2, IL1-β, IL-6, and TNF-ɑ were significantly higher in primary hypertension group and primary hypertension combined with hyperlipidemia group than those in the control group, with no significant difference in CCL2 levels among three groups (P 0.805, Table 3)
Summary
According to the latest clinical data, cardiovascular diseases have ranked first in prone diseases, causing 40% of the premature deaths of China’s population [1,2,3]. Hypertension and hyperlipemia are the most common diseases. Patients with hypertension account for about 43% of the total patients with cardiovascular diseases [4, 5], and patients with dyslipidemia accounting for 40.4% [6]. With the improvement of quality of life, hypertension combined with hyperlipemia has become the normal state for patients with cardiovascular diseases. Long-term hypertension and hyperlipemia can result in malignant diseases, such as stroke, myocardial infarction, renal failure, congestive heart failure, progressive atherosclerosis, and dementia [7]. Age, smoking, regulation of intestinal flora, lifestyle, and genetic determinism can all be taken as individual difference factors for the occurrence of hypertension combined with hyperlipemia. E complexity of influencing factors is one of the important reasons for its long-time Age, smoking, regulation of intestinal flora, lifestyle, and genetic determinism can all be taken as individual difference factors for the occurrence of hypertension combined with hyperlipemia. e complexity of influencing factors is one of the important reasons for its long-time
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