Exposure to cold aggravated pulmonary arterial hypertension (PAH) symptoms in an animal model of the disease, according to a new study published in Life Sciences.

The study showed that rats exposed to cold temperatures after being induced with PAH with monocrotaline (MCT) showed signs of right ventricular (RV) hypertrophy and increased thickness of the pulmonary arterial medial wall.

Rats in this group (MCT+Cold) also showed overexpression of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (IL-1β), and IL-6, compared to rats who had been given MCT but were not exposed to cold. The MCT+Cold group also had increased levels of messenger RNAs (mRNAs) including those expressed from Cd68 and Cd163.

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Increased expression of microRNAs (miRNAs) including miR-146a-5p and miR-155-5 was also observed in the lung tissue and plasma extracellular vesicles (EVs) of the MCT+Cold group. Exposure to cold also caused decreased expressions in the lungs of miR-21-5p as well as the mRNA of Bmpr2, Smad5, Tgfbr2, and Smad3.

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Cold exposure on its own without MCT treatment also caused increased hemodynamic factors such as mean and max pressure and end-systolic and end-diastolic volumes, compared to control rats who were kept at room temperature.

A higher percentage of pulmonary arterial medial wall thickness was also observed compared to control rats. Rats in this group showed trends toward changes in the expression of some mRNAs and miRNAs, however, they did not reach statistical significance.

“In conclusion, our findings provide evidence that cold exposure acts as a pro-inflammatory factor that, combined with MCT, exacerbates the PAH,” the authors concluded.

In the trial, a total of 24 male Sprague-Dawley rats were divided evenly into 4 groups: control, control plus exposure to cold (Cold), MCT-induced PAH (MCT), and MCT-induced PAH rats also exposed to cold (MCT+Cold). All rats were kept at room temperature (23.5 ± 2°C) for 3 weeks then the cold-exposed rats were transferred to cold rooms (5.0 ± 1°C) for 10 days.


Sánchez-Gloria JL, Carbó R, Buelna-Chontal M, et al. Cold exposure aggravates pulmonary arterial hypertension through increased miR-146a-5p, miR-155-5p and cytokines TNF-α, IL-1β, and IL-6. Life Sci. 2021;287(120091):120091. doi:10.1016/j.lfs.2021.120091